WorldWideScience

Sample records for diploid human lymphoblasts

  1. The diploid genome sequence of an individual human.

    Directory of Open Access Journals (Sweden)

    Samuel Levy

    2007-09-01

    Full Text Available Presented here is a genome sequence of an individual human. It was produced from approximately 32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel included 3,213,401 single nucleotide polymorphisms (SNPs, 53,823 block substitutions (2-206 bp, 292,102 heterozygous insertion/deletion events (indels(1-571 bp, 559,473 homozygous indels (1-82,711 bp, 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information.

  2. TRESK potassium channel in human T lymphoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Sánchez-Miguel, Dénison Selene, E-mail: amurusk@hotmail.com [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); García-Dolores, Fernando, E-mail: garciaddf@yahoo.com [Department of Pathology, Institute of Forensic Sciences, Av. Niños Héroes 130, Col. Doctores, C.P. 06720 Mexico, DF (Mexico); Rosa Flores-Márquez, María, E-mail: mariafo31@yahoo.com.mx [National Medical Center of Occident (CMNO) IMSS, Belisario Dominguez 735, Col. Independencia Oriente, C.P. 44340 Guadalajara, Jalisco (Mexico); Delgado-Enciso, Iván [University of Colima, School of Medicine, Av. Universidad 333, Col. Las Viboras, C.P. 28040 Colima (Mexico); Pottosin, Igor, E-mail: pottosin@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); Dobrovinskaya, Oxana, E-mail: oxana@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico)

    2013-05-03

    Highlights: • TRESK (KCNK18) mRNA is present in different T lymphoblastic cell lines. • KCNK18 mRNA was not found in resting peripheral blood lymphocytes. • Clinical samples of T lymphoblastic leukemias and lymphomas were positive for TRESK. • TRESK in T lymphoblasts has dual localization, in plasma membrane and intracellular. -- Abstract: TRESK (TWIK-related spinal cord K{sup +}) channel, encoded by KCNK18 gene, belongs to the double-pore domain K{sup +} channel family and in normal conditions is expressed predominantly in the central nervous system. In our previous patch-clamp study on Jurkat T lymphoblasts we have characterized highly selective K{sup +} channel with pharmacological profile identical to TRESK. In the present work, the presence of KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but not in resting peripheral blood lymphocytes of healthy donors. Positive immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane, intracellular TRESK localization was also revealed. Possible involvement of TRESK channel in lymphocyte proliferation and tumorigenesis is discussed.

  3. Aminoguanidine delays the replicative senescence of human diploid fibroblasts

    Institute of Scientific and Technical Information of China (English)

    WANG Pei-chang; ZHANG Jian; ZHANG Zong-yu; TONG Tan-jun

    2007-01-01

    advanced glycation end products; comet assayBackground The accumulation of free radicals and advanced glycation end products (AGEs) in cell plays a very important role in replicative senescence. Aminoguanidine (AG) has potential antioxidant effects and decreases AGE levels. This study aimed to investigate its effect on replicative senescence in vitro.Methods The effects of aminoguanidine on morphology, replicative lifespan, cell growth and proliferation, AGEs, DNA damage, DNA repair ability and telomere length were observed in human fetal lung diploid fibroblasts (2BS).Results Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late population doubling (PD) and increased cumulative population doublings by at least 17-21 PDs. Aminoguanidine also improved the potentials of growth and proliferation of 2BS cells as detected by the MTT assay. The AGE levels of late PD cells grown from early PD in DMEM containing aminiguanidine decreased significantly compared with those of late PD control cells and were similar to those of young control cells. In addition, the cells pretreated with aminoguanidine had a significant reduction in DNA strand breaks when they were exposed to 200 μmol/L H2O2 for 5 minutes which indicated that the compound had a strong potential to protect genomic DNA against oxidative stress. And most of the cells exposed to 100 μmol/L H2O2 had much shorter comet tails and smaller tail areas after incubation with aminoguanidine-supplemented DMEM, which indicated that the compound strongly improved the DNA repair abilities of 2BS cells. Moreover, PD55 cells grown from PD28 in 2 mmol/L or 4 mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb, which was 0.83 kb or 1.11kb longer than that of the control cells.Conclusion Aminoguanidine delays replicative senescence of 2BS cells and the senescence-delaying effect of aminoguanidine appear to be due to its many biological properties including its potential for proliferation

  4. Diploid, but not haploid, human embryonic stem cells can be derived from microsurgically repaired tripronuclear human zygotes.

    Science.gov (United States)

    Fan, Yong; Li, Rong; Huang, Jin; Yu, Yang; Qiao, Jie

    2013-01-15

    Human embryonic stem cells have shown tremendous potential in regenerative medicine, and the recent progress in haploid embryonic stem cells provides new insights for future applications of embryonic stem cells. Disruption of normal fertilized embryos remains controversial; thus, the development of a new source for human embryonic stem cells is important for their usefulness. Here, we investigated the feasibility of haploid and diploid embryo reconstruction and embryonic stem cell derivation using microsurgically repaired tripronuclear human zygotes. Diploid and haploid zygotes were successfully reconstructed, but a large proportion of them still had a tripolar spindle assembly. The reconstructed embryos developed to the blastocyst stage, although the loss of chromosomes was observed in these zygotes. Finally, triploid and diploid human embryonic stem cells were derived from tripronuclear and reconstructed zygotes (from which only one pronucleus was removed), but haploid human embryonic stem cells were not successfully derived from the reconstructed zygotes when two pronuclei were removed. Both triploid and diploid human embryonic stem cells showed the general characteristics of human embryonic stem cells. These results indicate that the lower embryo quality resulting from abnormal spindle assembly contributed to the failure of the haploid embryonic stem cell derivation. However, the successful derivation of diploid embryonic stem cells demonstrated that microsurgical tripronuclear zygotes are an alternative source of human embryonic stem cells. In the future, improving spindle assembly will facilitate the application of triploid zygotes to the field of haploid embryonic stem cells.

  5. The Effect of Prolonged Culture of Chromosomally Abnormal Human Embryos on The Rate of Diploid Cells

    Directory of Open Access Journals (Sweden)

    Masood Bazrgar

    2016-12-01

    Full Text Available Background: A decrease in aneuploidy rate following a prolonged co-culture of human blastocysts has been reported. As co-culture is not routinely used in assisted reproductive technology, the present study aimed to evaluate the effect of the prolonged single culture on the rate of diploid cells in human embryos with aneuploidies. Materials and Methods: In this cohort study, we used fluorescence in situ hybridization (FISH to reanalyze surplus blastocysts undergoing preimplantation genetic diagnosis (PGD on day 3 postfertilization. They were randomly studied on days 6 or 7 following fertilization. Results: Of the 30 analyzed blastocysts, mosaicism was observed in 26(86.6%, while 2(6.7% were diploid, and 2(6.7% were triploid. Of those with mosaicism, 23(88.5% were determined to be diploid-aneuploid and 3(11.5% were aneuploid mosaic. The total frequency of embryos with more than 50% diploid cells was 33.3% that was lower on day 7 in comparison with the related value on day 6 (P<0.05; however, there were no differences when the embryos were classified according to maternal age, blastocyst developmental stage, total cell number on day 3, and embryo quality. Conclusion: Although mosaicism is frequently observed in blastocysts, the prolonged single culture of blastocysts does not seem to increase the rate of normal cells.

  6. Gelam Honey Protects against Gamma-Irradiation Damage to Antioxidant Enzymes in Human Diploid Fibroblasts

    OpenAIRE

    Suzana Makpol; Tengku Ahbrizal Farizal Tengku Ahmad; Yasmin Anum Mohd Yusof; Nor Fadilah Rajab; Khairuddin Abdul Rahim; Zakiah Jubri

    2013-01-01

    The present study was designed to determine the radioprotective effects of Malaysian Gelam honey on gene expression and enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) of human diploid fibroblasts (HDFs) subjected to gamma-irradiation. Six groups of HDFs were studied: untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/mL of sterilized Gelam ...

  7. Effect of cell cycle inhibitor p19ARF on senescence of human diploid cell

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To investigate the effect of cell cycle inhibitor p19ARF on replicative senescence of human diploid cell, recombinant p19ARF eukaryotic expression vector was constructed and p19ARF gene was transfected into human diploid fibroblasts (WI-38 cells) by liposome-mediated transfection for overexpression. Then, the effects of p19ARF on replicative senescence of WI-38 cells were observed. The results re- vealed that, compared with control cells, the WI-38 cells in which p19ARF gene was introduced showed significant up-regulation of p53 and p21 expression level, decrease of cell generation by 10 12 generations, decline of cell growth rate with cell cycle being arrested at G1 phase, increase of positive rate of senescent marker SA-β-gal staining, and decrease of mitochondrial membrane potential. The morphology of the transfected fibroblasts presented the characteristics changes similar to senescent cells. These results indicated that high expression of p19ARF may promote the senescent process of human diploid cells.

  8. Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells.

    Science.gov (United States)

    Yamada, Mitsutoshi; Johannesson, Bjarki; Sagi, Ido; Burnett, Lisa Cole; Kort, Daniel H; Prosser, Robert W; Paull, Daniel; Nestor, Michael W; Freeby, Matthew; Greenberg, Ellen; Goland, Robin S; Leibel, Rudolph L; Solomon, Susan L; Benvenisty, Nissim; Sauer, Mark V; Egli, Dieter

    2014-06-26

    The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.

  9. Assembly and diploid architecture of an individual human genome via single-molecule technologies.

    Science.gov (United States)

    Pendleton, Matthew; Sebra, Robert; Pang, Andy Wing Chun; Ummat, Ajay; Franzen, Oscar; Rausch, Tobias; Stütz, Adrian M; Stedman, William; Anantharaman, Thomas; Hastie, Alex; Dai, Heng; Fritz, Markus Hsi-Yang; Cao, Han; Cohain, Ariella; Deikus, Gintaras; Durrett, Russell E; Blanchard, Scott C; Altman, Roger; Chin, Chen-Shan; Guo, Yan; Paxinos, Ellen E; Korbel, Jan O; Darnell, Robert B; McCombie, W Richard; Kwok, Pui-Yan; Mason, Christopher E; Schadt, Eric E; Bashir, Ali

    2015-08-01

    We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.

  10. Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes.

    Directory of Open Access Journals (Sweden)

    Mark Lipson

    2015-11-01

    Full Text Available The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Most notably, recent approaches based on counting de novo mutations in family pedigrees have yielded significantly smaller values than classical methods based on sequence divergence. Here, we propose a new method that uses the fine-scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long-term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.61 ± 0.13 × 10-8 mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes.

  11. Effects of Antioxidants and Vitamins on the Proliferation of Human Diploid Cells

    Directory of Open Access Journals (Sweden)

    Gaziza Dаnlybaeva

    2014-01-01

    Full Text Available Introduction: Microelements, essential nutrients that are needed in small amounts including minerals such as calcium, zinc, iron and other vitamins (A, B, C, and etc., are macronutrients necessary for a healthy life. The role of micronutrients in vivo is well known, and there are several publications that have examined the effects of micronutrients on genomic stability. Furthermore, a number of vitamins and microelements are substrates and/or cofactors in metabolic pathways, which regulate DNA synthesis and/or repair and gene expression. A deficiency in such nutrients may result in disruption of genomic integrity and alterations in DNA methylation patterns, linking cellular nutrition with change in gene expression. For example, lack of vitamin C is known to cause increased DNA oxidation and chromosomal damage. Vitamin A, as well as other micronutrients, have a protective effect, whereas higher concentrations are associated with increased DNA damage. Ubiquinone (coenzyme Q10 and dihydroquercetin are used in therapy as antioxidant compounds and electron carriers, which reduce lipid peroxidation of cell membranes. However, previous studies indicate that various ubiquinone analogs may cause a divergent effect on oxidative stress and oxidative phosphorylation. The aim of our study was to investigate the effect of vitamins A and C, coenzyme Q10, and dihydroquercetin on the proliferative potential of cultured human embryonic diploid fibroblasts (M-22. Methods: In the first series of experiments, nontoxic concentrations of vitamins for the cells were identified using MTT assay. Results: Vitamins A and C, dihydroquercetin of 1µM, and coenzyme Q10 of 5µM were nontoxic for human skin fibroblasts. In the second series of experiments, cell cultivation was carried out with nontoxic concentrations. A vitamin C concentration of 1µM for 7 consecutive passages increased the proliferation index (PI compared to the control. Thus, the average PI in the

  12. Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts

    Directory of Open Access Journals (Sweden)

    Masatoshi Suzuki

    2012-01-01

    Full Text Available Foci of phosphorylated histone H2AX and ATM are the surrogate markers of DNA double strand breaks. We previously reported that the residual foci increased their size after irradiation, which amplifies DNA damage signals. Here, we addressed whether amplification of DNA damage signal is involved in replicative senescence of normal human diploid fibroblasts. Large phosphorylated H2AX foci (>1.5 μm diameter were specifically detected in presenescent cells. The frequency of cells with large foci was well correlated with that of cells positive for senescence-associated β-galactosidase staining. Hypoxic cell culture condition extended replicative life span of normal human fibroblast, and we found that the formation of large foci delayed in those cells. Our immuno-FISH analysis revealed that large foci partially localized at telomeres in senescent cells. Importantly, large foci of phosphorylated H2AX were always colocalized with phosphorylated ATM foci. Furthermore, Ser15-phosphorylated p53 showed colocalization with the large foci. Since the treatment of senescent cells with phosphoinositide 3-kinase inhibitor, wortmannin, suppressed p53 phosphorylation, it is suggested that amplification of DNA damage signaling sustains persistent activation of ATM-p53 pathway, which is essential for replicative senescence.

  13. Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts

    Science.gov (United States)

    Sklirou, Aimilia D.; Ralli, Marianna; Dominguez, Maria; Papassideri, Issidora; Skaltsounis, Alexios-Leandros; Trougakos, Ioannis P.

    2015-01-01

    Despite the fact that several natural products (e.g. crude extracts or purified compounds) have been found to activate cell antioxidant responses and/or delay cellular senescence the effect(s) of small peptides on cell viability and/or modulation of protective mechanisms (e.g. the proteostasis network) remain largely elusive. We have thus studied a hexapeptide (Hexapeptide-11) of structure Phe–Val–Ala–Pro–Phe–Pro (FVAPFP) originally isolated from yeast extracts and later synthesized by solid state synthesis to high purity. We show herein that Hexapeptide-11 exhibits no significant toxicity in normal human diploid lung or skin fibroblasts. Exposure of fibroblasts to Hexapeptide-11 promoted dose and time-dependent activation of proteasome, autophagy, chaperones and antioxidant responses related genes. Moreover, it promoted increased nuclear accumulation of Nrf2; higher expression levels of proteasomal protein subunits and increased proteasome peptidase activities. In line with these findings we noted that Hexapeptide-11 conferred significant protection in fibroblasts against oxidative-stress-mediated premature cellular senescence, while at in vivo skin deformation assays in human subjects it improved skin elasticity. Finally, Hexapeptide-11 was found to induce the activity of extracellular MMPs and it also suppressed cell migration. Our presented findings indicate that Hexapeptide-11 is a promising anti-ageing agent. PMID:25974626

  14. Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts

    Directory of Open Access Journals (Sweden)

    Aimilia D. Sklirou

    2015-08-01

    Full Text Available Despite the fact that several natural products (e.g. crude extracts or purified compounds have been found to activate cell antioxidant responses and/or delay cellular senescence the effect(s of small peptides on cell viability and/or modulation of protective mechanisms (e.g. the proteostasis network remain largely elusive. We have thus studied a hexapeptide (Hexapeptide-11 of structure Phe–Val–Ala–Pro–Phe–Pro (FVAPFP originally isolated from yeast extracts and later synthesized by solid state synthesis to high purity. We show herein that Hexapeptide-11 exhibits no significant toxicity in normal human diploid lung or skin fibroblasts. Exposure of fibroblasts to Hexapeptide-11 promoted dose and time-dependent activation of proteasome, autophagy, chaperones and antioxidant responses related genes. Moreover, it promoted increased nuclear accumulation of Nrf2; higher expression levels of proteasomal protein subunits and increased proteasome peptidase activities. In line with these findings we noted that Hexapeptide-11 conferred significant protection in fibroblasts against oxidative-stress-mediated premature cellular senescence, while at in vivo skin deformation assays in human subjects it improved skin elasticity. Finally, Hexapeptide-11 was found to induce the activity of extracellular MMPs and it also suppressed cell migration. Our presented findings indicate that Hexapeptide-11 is a promising anti-ageing agent.

  15. Effects of Captan on DNA and DNA metabolic processes in human diploid fibroblasts.

    Science.gov (United States)

    Snyder, R D

    1992-01-01

    The fungicide Captan has been examined for its effects on DNA and DNA processing in order to better understand the genotoxicity associated with this agent. Captan treatment resulted in production of DNA single strand breaks and DNA-protein cross-links and elicited an excision repair response in human diploid fibroblasts. Captan was also shown to inhibit cellular DNA synthesis and to form stable adducts in herring sperm and human cellular DNA. Misincorporation of nucleotides into Captan-treated synthetic DNA templates was significantly elevated in an in vitro assay using E. coli DNA polymerase I, suggesting that DNA adduct formation by Captan could have mutagenic consequences. In sum, these studies demonstrate that Captan is capable of interacting with DNA at a number of levels and that these interactions could provide the basis for Captan's genotoxicity. The extreme cytotoxicity of this fungicide, however, could be due to other cellular effects since at the IC50 for cell killing, approximately 0.8 microM, none of the above genotoxic events could be detected by the methods employed.

  16. Piper betle L. Modulates Senescence-Associated Genes Expression in Replicative Senescent Human Diploid Fibroblasts

    Directory of Open Access Journals (Sweden)

    Lina Wati Durani

    2017-01-01

    Full Text Available Piper betle (PB is a traditional medicine that is widely used to treat different diseases around Asian region. The leaf extracts contain various bioactive compounds, which were reported to have antidiabetic, antibacterial, anti-inflammatory, antioxidant, and anticancer effects. In this study, the effect of PB aqueous extracts on replicative senescent human diploid fibroblasts (HDFs was investigated by determining the expressions of senescence-associated genes using quantitative PCR. Our results showed that PB extracts at 0.4 mg/ml can improve cell proliferation of young (143%, presenescent (127.3%, and senescent (157.3% HDFs. Increased expressions of PRDX6, TP53, CDKN2A, PAK2, and MAPK14 were observed in senescent HDFs compared to young and/or presenescent HDFs. Treatment with PB extracts modulates the transcriptional profile changes in senescent HDFs. By contrast, expressions of SOD1 increased, whereas GPX1, PRDX6, TP53, CDKN2A, PAK2, and MAPK14 were decreased in PB-treated senescent HDFs compared to untreated senescent HDFs. In conclusion, this study indicates the modulation of PB extracts on senescence-associated genes expression of replicative senescent HDFs. Further studies warrant determining the mechanism of PB in modulating replicative senescence of HDFs through these signaling pathways.

  17. Modulation of Cell Cycle Profile by Chlorella vulgaris Prevents Replicative Senescence of Human Diploid Fibroblasts

    Directory of Open Access Journals (Sweden)

    Tayyebeh Saberbaghi

    2013-01-01

    Full Text Available In this study, the effects of Chlorella vulgaris (CV on replicative senescence of human diploid fibroblasts (HDFs were investigated. Hot water extract of CV was used to treat HDFs at passages 6, 15, and 30 which represent young, presenescence, and senescence ages, respectively. The level of DNA damage was determined by comet assay while apoptosis and cell cycle profile were determined using FACSCalibur flow cytometer. Our results showed direct correlation between increased levels of damaged DNA and apoptosis with senescence in untreated HDFs (P<0.05. Cell cycle profile showed increased population of untreated senescent cells that enter G0/G1 phase while the cell population in S phase decreased significantly (P<0.05. Treatment with CV however caused a significant reduction in the level of damaged DNA and apoptosis in all age groups of HDFs (P<0.05. Cell cycle analysis showed that treatment with CV increased significantly the percentage of senescent HDFs in S phase and G2/M phases but decreased the population of cells in G0/G1 phase (P<0.05. In conclusion, hot water extract of Chlorella vulgaris effectively decreased the biomarkers of ageing, indicating its potential as an antiageing compound.

  18. Phosphatidylinositol 3-kinase inhibitor, LY294002, induced senescence-like changes in human diploid fibroblasts

    Institute of Scientific and Technical Information of China (English)

    李淑萍; 张宗玉; 童坦君

    2003-01-01

    Objective To reveal the role of Phosphatidylinositol 3-kinases (PI3Ks) in regulating human diploid fibroblast (2BS cell) senescence as well as the possible mechanisms involved.Methods Using a PI3Ks specific inhibitor, LY294002, cell cycle, apoptosis, proliferation, senescence association β-galactosidase staining as well as senescence association CKIs, p16 INK4 and p21 Cip1 protein expressions were all measured in the low passages of 2BS cells.Results Both 25 μmol/L and 50 μmol/L concentrations of LY294002 could cause a significant decrease in cells entering into S phase, and this cell cycle of G 1 phase arrest was dose-dependent. Meanwhile, LY294002 contributed to apoptosis, caused 2BS cell growth arrest, and activated senescence association β-galactosidase (P<0.05). In addition, LY294002 could induce time-course expressions of p16 INK4 and p21 Cip1 in 2BS cell lines.Conclusions PI3Ks inhibitor LY294002 could induce senescence-like changes in 2BS cell lines. Two enescence associated CKIs,p16 INK4 and p21 Cip1, might be involved in this senescence phenotype proceeding in 2BS cell lines.

  19. Gelam Honey Protects against Gamma-Irradiation Damage to Antioxidant Enzymes in Human Diploid Fibroblasts

    Directory of Open Access Journals (Sweden)

    Suzana Makpol

    2013-02-01

    Full Text Available The present study was designed to determine the radioprotective effects of Malaysian Gelam honey on gene expression and enzyme activity of superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GPx of human diploid fibroblasts (HDFs subjected to gamma-irradiation. Six groups of HDFs were studied: untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/mL of sterilized Gelam honey (w/v for 24 h and exposed to 1 Gray (Gy of gamma rays at the dose rate of 0.25 Gy/min. Gamma-irradiation was shown to down-regulate SOD1, SOD2, CAT and GPx1 gene expressions (p < 0.05. Conversely, HDFs treated with Gelam honey alone showed up-regulation of all genes studied. Similarly, SOD, CAT and GPx enzyme activities in HDFs decreased with gamma-irradiation and increased when cells were treated with Gelam honey (p < 0.05. Furthermore, of the three different stages of study treatment, pre-treatment with Gelam honey caused up-regulation of SOD1, SOD2 and CAT genes expression and increased the activity of SOD and CAT. As a conclusion, Gelam honey modulates the expression of antioxidant enzymes at gene and protein levels in irradiated HDFs indicating its potential as a radioprotectant agent.

  20. Modulation of Cell Cycle Profile by Chlorella vulgaris Prevents Replicative Senescence of Human Diploid Fibroblasts.

    Science.gov (United States)

    Saberbaghi, Tayyebeh; Abbasian, Firouz; Mohd Yusof, Yasmin Anum; Makpol, Suzana

    2013-01-01

    In this study, the effects of Chlorella vulgaris (CV) on replicative senescence of human diploid fibroblasts (HDFs) were investigated. Hot water extract of CV was used to treat HDFs at passages 6, 15, and 30 which represent young, presenescence, and senescence ages, respectively. The level of DNA damage was determined by comet assay while apoptosis and cell cycle profile were determined using FACSCalibur flow cytometer. Our results showed direct correlation between increased levels of damaged DNA and apoptosis with senescence in untreated HDFs (P < 0.05). Cell cycle profile showed increased population of untreated senescent cells that enter G0/G1 phase while the cell population in S phase decreased significantly (P < 0.05). Treatment with CV however caused a significant reduction in the level of damaged DNA and apoptosis in all age groups of HDFs (P < 0.05). Cell cycle analysis showed that treatment with CV increased significantly the percentage of senescent HDFs in S phase and G2/M phases but decreased the population of cells in G0/G1 phase (P < 0.05). In conclusion, hot water extract of Chlorella vulgaris effectively decreased the biomarkers of ageing, indicating its potential as an antiageing compound.

  1. Transformation and radiosensitivity of human diploid skin fibroblasts transfected with activated RAS oncogene and SV40 T-antigen

    Energy Technology Data Exchange (ETDEWEB)

    Su, L.-N.; Little, J.B. (Harvard School of Public Health, Boston, MA (United States))

    1992-08-01

    Three normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) or SV40 T-antigen. Multiple clones were examined for morphological alterations, growth requirements, ability to grow under anchorage independent conditions, immortality and tumorigenicity in nude mice. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant as compared with their parent cells or clones transfected with the neo gene only. This radioresistant phenotype persisted in post-crisis, immortalized cell lines. These data suggest that expression of the SV40 T-antigen but not activated Ha-ras plays an important role in the radiosensitivity of human diploid cells. The radioresistant phenotype in SV40 T transfected cells was not related to the enhanced level of genetic instability seen in pre-crisis and newly immortalized cells, nor to the process of immortalization itself. (author).

  2. Fetal calf serum heat inactivation and lipopolysaccharide contamination influence the human T lymphoblast proteome and phosphoproteome

    Directory of Open Access Journals (Sweden)

    Rahman Hazir

    2011-11-01

    Full Text Available Abstract Background The effects of fetal calf serum (FCS heat inactivation and bacterial lipopolysaccharide (LPS contamination on cell physiology have been studied, but their effect on the proteome of cultured cells has yet to be described. This study was undertaken to investigate the effects of heat inactivation of FCS and LPS contamination on the human T lymphoblast proteome. Human T lymphoblastic leukaemia (CCRF-CEM cells were grown in FCS, either non-heated, or heat inactivated, having low ( Results A total of four proteins (EIF3M, PRS7, PSB4, and SNAPA were up-regulated when CCRF-CEM cells were grown in media supplemented with heat inactivated FCS (HE as compared to cells grown in media with non-heated FCS (NHE. Six proteins (TCPD, ACTA, NACA, TCTP, ACTB, and ICLN displayed a differential phosphorylation pattern between the NHE and HE groups. Compared to the low concentration LPS group, regular levels of LPS resulted in the up-regulation of three proteins (SYBF, QCR1, and SUCB1. Conclusion The present study provides new information regarding the effect of FCS heat inactivation and change in FCS-LPS concentration on cellular protein expression, and post-translational modification in human T lymphoblasts. Both heat inactivation and LPS contamination of FCS were shown to modulate the expression and phosphorylation of proteins involved in basic cellular functions, such as protein synthesis, cytoskeleton stability, oxidative stress regulation and apoptosis. Hence, the study emphasizes the need to consider both heat inactivation and LPS contamination of FCS as factors that can influence the T lymphoblast proteome.

  3. Frequency of chromosomally-integrated human herpesvirus 6 in children with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Annie Gravel

    Full Text Available INTRODUCTION: Human herpesvirus 6 (HHV-6 is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6. The biological consequences of chromosomal integration by HHV-6 remain unknown. OBJECTIVE: To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors. METHODOLOGY: A total of 293 DNA samples from children with pre-B (n=255, pre-pre-B (n=4, pre-T (n=26 and undetermined (n=8 leukemia were analyzed for ciHHV-6 by quantitative TaqMan PCR (QPCR using HHV-6 specific primers and probe. As control, DNA samples from 288 healthy individuals were used. Primers and probe specific to the cellular GAPDH gene were used to estimate integrity and DNA content. RESULTS: Out of 293 DNA samples from the leukemic cohort, 287 contained amplifiable DNA. Of these, only 1 (0.35% contained ciHHV-6. Variant typing indicates that the ci-HHV-6 corresponds to variant A. None of the 288 DNA samples from healthy individuals contained ciHHV-6. CONCLUSION: The frequency of ciHHV-6 in children with acute lymphoblastic leukemia is similar (p=0.5 to that of healthy individuals. These results suggest that acute lymphoblastic leukemia does not originate as a consequence to integration of HHV-6 within the chromosomes.

  4. Sp1 is essential for p16 expression in human diploid fibroblasts during senescence.

    Directory of Open Access Journals (Sweden)

    Junfeng Wu

    Full Text Available BACKGROUND: p16(INK4a tumor suppressor protein has been widely proposed to mediate entrance of the cells into the senescent stage. Promoter of p16(INK4a gene contains at least five putative GC boxes, named GC-I to V, respectively. Our previous data showed that a potential Sp1 binding site, within the promoter region from -466 to -451, acts as a positive transcription regulatory element. These results led us to examine how Sp1 and/or Sp3 act on these GC boxes during aging in cultured human diploid fibroblasts. METHODOLOGY/PRINCIPAL FINDINGS: Mutagenesis studies revealed that GC-I, II and IV, especially GC-II, are essential for p16(INK4a gene expression in senescent cells. Electrophoretic mobility shift assays (EMSA and ChIP assays demonstrated that both Sp1 and Sp3 bind to these elements and the binding activity is enhanced in senescent cells. Ectopic overexpression of Sp1, but not Sp3, induced the transcription of p16(INK4a. Both Sp1 RNAi and Mithramycin, a DNA intercalating agent that interferes with Sp1 and Sp3 binding activities, reduced p16(INK4a gene expression. In addition, the enhanced binding of Sp1 to p16(INK4a promoter during cellular senescence appeared to be the result of increased Sp1 binding affinity, not an alteration in Sp1 protein level. CONCLUSIONS/SIGNIFICANCE: All these results suggest that GC- II is the key site for Sp1 binding and increase of Sp1 binding activity rather than protein levels contributes to the induction of p16(INK4a expression during cell aging.

  5. Molecular evolution of hepatitis A virus in a human diploid cell line

    Institute of Scientific and Technical Information of China (English)

    Cai-Hua Tang; Jiang-Sen Mao; Shao-Ai Chai; Yong Chen; Fang-Cheng Zhuang

    2007-01-01

    AIM: To investigate the hotspots, direction, and the time course of evolution of hepatitis A virus in the process of consecutive cell culture passage in human KMB17 diploid cells.METHODS: Wild type hepatitis A virus H2w was serially propagated in KMB17 cells until passage 30, and the full-length genomes of H2w and its six chosen progenies were determined by directly sequencing RT-PCR products amplified from viral genomic RNA. Alignment comparison of sequences from H2w with its six progenies and phylogenetic analysis of the whole VP1 region from H2w, progenies of H2w, and other cell culture adapted hepatitis A virus were then carried out to obtain data on the molecular evolution of hepatitis A virus in the process of consecutive passage in KMB17 cells.RESULTS: Most of the mutations occurred by passage 5 and several hotspots related to adaptation of the virus during cell growth were observed. After that stage, few additional mutations occurred through the remaining duration of passage in KMB17 cells except for mutation in the virulence determinants, which occurred in the vicinity of passage 15. The phylogenetic analysis of the whole VP1 region suggested that the progenies of H2w evolved closely to other cell culture adapted hepatitis A virus, i.e. MBB, L-A-1, other than its progenitor H2w.CONCLUSION: Hepatitis A virus served as a useful model for studying molecular evolution of viruses in a given environment. The information obtained in this study may provide assistance in cultivating the next generation of a seed virus for live hepatitis A vaccine production.

  6. Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's Disease human lymphoblasts.

    Science.gov (United States)

    Naia, Luana; Ferreira, I Luísa; Cunha-Oliveira, Teresa; Duarte, Ana I; Ribeiro, Márcio; Rosenstock, Tatiana R; Laço, Mário N; Ribeiro, Maria J; Oliveira, Catarina R; Saudou, Frédéric; Humbert, Sandrine; Rego, A Cristina

    2015-02-01

    Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Mitochondrial dysfunction associated with energy failure plays an important role in this untreated pathology. In the present work, we used lymphoblasts obtained from HD patients or unaffected parentally related individuals to study the protective role of insulin-like growth factor 1 (IGF-1) versus insulin (at low nM) on signaling and metabolic and mitochondrial functions. Deregulation of intracellular signaling pathways linked to activation of insulin and IGF-1 receptors (IR,IGF-1R), Akt, and ERK was largely restored by IGF-1 and, at a less extent, by insulin in HD human lymphoblasts. Importantly, both neurotrophic factors stimulated huntingtin phosphorylation at Ser421 in HD cells. IGF-1 and insulin also rescued energy levels in HD peripheral cells, as evaluated by increased ATP and phosphocreatine, and decreased lactate levels. Moreover, IGF-1 effectively ameliorated O2 consumption and mitochondrial membrane potential (Δψm) in HD lymphoblasts, which occurred concomitantly with increased levels of cytochrome c. Indeed, constitutive phosphorylation of huntingtin was able to restore the Δψm in lymphoblasts expressing an abnormal expansion of polyglutamines. HD lymphoblasts further exhibited increased intracellular Ca(2+) levels before and after exposure to hydrogen peroxide (H2O2), and decreased mitochondrial Ca(2+) accumulation, being the later recovered by IGF-1 and insulin in HD lymphoblasts pre-exposed to H2O2. In summary, the data support an important role for IR/IGF-1R mediated activation of signaling pathways and improved mitochondrial and metabolic function in HD human lymphoblasts.

  7. SIRT1 overexpression antagonizes cellular senescence with activated ERK/S6k1 signaling in human diploid fibroblasts.

    Directory of Open Access Journals (Sweden)

    Jing Huang

    Full Text Available Sir2, a NAD-dependent deacetylase, modulates lifespan in yeasts, worms and flies. The SIRT1, mammalian homologue of Sir2, regulates signaling for favoring survival in stress. But whether SIRT1 has the function to influence cell viability and senescence under non-stressed conditions in human diploid fibroblasts is far from unknown. Our data showed that enforced SIRT1 expression promoted cell proliferation and antagonized cellular senescence with the characteristic features of delayed Senescence-Associated beta-galactosidase (SA-beta-gal staining, reduced Senescence-Associated Heterochromatic Foci (SAHF formation and G1 phase arrest, increased cell growth rate and extended cellular lifespan in human fibroblasts, while dominant-negative SIRT1 allele (H363Y did not significantly affect cell growth and senescence but displayed a bit decreased lifespan. Western blot results showed that SIRT1 reduced the expression of p16(INK4A and promoted phosphorylation of Rb. Our data also exposed that overexpression of SIRT1 was accompanied by enhanced activation of ERK and S6K1 signaling. These effects were mimicked in both WI38 cells and 2BS cells by concentration-dependent resveratrol, a SIRT1 activator. It was noted that treatment of SIRT1-.transfected cells with Rapamycin, a mTOR inhibitor, reduced the phosphorylation of S6K1 and the expression of Id1, implying that SIRT1-induced phosphorylation of S6K1 may be partly for the decreased expression of p16(INK4A and promoted phosphorylation of Rb in 2BS. It was also observed that the expression of SIRT1 and phosphorylation of ERK and S6K1 was declined in senescent 2BS. These findings suggested that SIRT1-promoted cell proliferation and antagonized cellular senescence in human diploid fibroblasts may be, in part, via the activation of ERK/ S6K1 signaling.

  8. X-ray sensitivity of fifty-three human diploid fibroblast cell strains from patients with characterized genetic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Weichselbaum, R.R.; Nove, J.; Little, J.B.

    1980-03-01

    The in vitro response of 53 human diploid fibroblast strains to x-irradiation was studied using a clonogenic survival assay. The strains, derived from patients with a variety of characterized clinical conditions, most with a genetic component, ranged in Do (a measure of the slope of the survival curve) from 43 to 168 rads. The mean Do's of six strains from normal individuals was 140 to 152 rads, with an overall range, based on the extremes of their standard errors, of 128 to 164 rads. Three-quarters of the strains studied fell within this range. Strains identified as sensitive came from patients with ataxia telangiectasia, progeria, the two genetic forms of retinoblastoma, and partial trisomy of chromosome 13. No marked radiosensitivity was found among strains derived from patients with a number of other conditions associated with a predisposition to malignancy.

  9. Effect of experimental treatment on GAPDH mRNA expression as a housekeeping gene in human diploid fibroblasts

    Directory of Open Access Journals (Sweden)

    Zainuddin Azalina

    2010-08-01

    Full Text Available Abstract Background Several genes have been used as housekeeping genes and choosing an appropriate reference gene is important for accurate quantitative RNA expression in real time RT-PCR technique. The expression levels of reference genes should remain constant between the cells of different tissues and under different experimental conditions. The purpose of this study was to determine the effect of different experimental treatments on the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH mRNA so that the reliability of GAPDH as reference gene for quantitative real time RT-PCR in human diploid fibroblasts (HDFs can be validated. HDFs in 4 different treatment groups viz; young (passage 4, senescent (passage 30, H2O2-induced oxidative stress and γ-tocotrienol (GTT-treated groups were harvested for total RNA extraction. Total RNA concentration and purity were determined prior to GAPDH mRNA quantification. Standard curve of GAPDH expression in serial diluted total RNA, melting curve analysis and agarose gel electrophoresis were used to determine the reliability of GAPDH as reference gene. Results HDFs with different experimental treatments exhibited diverse cell morphology with different expression of senescence-associated β-galactosidase (SA β-gal activity. However the expression level of GAPDH was consistent in all treatment groups. Conclusion The study demonstrated that GAPDH is reliable as reference gene for quantitative gene expression analysis in HDFs. Therefore it can be used as housekeeping gene for quantitative real time RT-PCR technique in human diploid fibroblasts particularly in studying cellular senescence.

  10. New sequence-based data on the relative DNA contents of chromosomes in the normal male and female human diploid genomes for radiation molecular cytogenetics

    Directory of Open Access Journals (Sweden)

    Repin Mikhail V

    2009-06-01

    Full Text Available Abstract Background The objective of this work is to obtain the correct relative DNA contents of chromosomes in the normal male and female human diploid genomes for the use at FISH analysis of radiation-induced chromosome aberrations. Results The relative DNA contents of chromosomes in the male and female human diploid genomes have been calculated from the publicly available international Human Genome Project data. New sequence-based data on the relative DNA contents of human chromosomes were compared with the data recommended by the International Atomic Energy Agency in 2001. The differences in the values of the relative DNA contents of chromosomes obtained by using different approaches for 15 human chromosomes, mainly for large chromosomes, were below 2%. For the chromosomes 13, 17, 20 and 22 the differences were above 5%. Conclusion New sequence-based data on the relative DNA contents of chromosomes in the normal male and female human diploid genomes were obtained. This approach, based on the genome sequence, can be recommended for the use in radiation molecular cytogenetics.

  11. Antiaging Effect of Pine Pollen in Human Diploid Fibroblasts and in a Mouse Model Induced by D-Galactose

    Directory of Open Access Journals (Sweden)

    Gen-Xiang Mao

    2012-01-01

    Full Text Available The present paper was designed to investigate the effect of pine pollen against aging in human diploid fibroblast 2BS cells and in an accelerated aging model, which was established by subcutaneous injections with D-galactose daily for 8 weeks in C57BL/6J mice. Pine pollen (1 mg/mL and 2 mg/mL is proved to delay the replicative senescence of 2BS cells as evidenced by enhanced cell proliferation, decreased SA-β-Gal activity, and reversed expression of senescence-associated molecular markers, such as p53, p21Waf1, p16INK4a, PTEN, and p27Kip1 in late PD cells. Besides, pine pollen reversed D-galactose-induced aging effects in neural activity and inflammatory cytokine levels, as indicated by improved memory latency time and reduced error rate in step-down test and decreased concentrations of IL-6 and TNF-α in model mice. Similar to the role of AGEs (advanced glycation endproducts formation inhibitor aminoguanidine (AG, pine pollen inhibited D-galactose-induced increment of AGEs levels thus reversed the aging phenotypes in model mice. Furthermore, the declined antioxidant activity was obviously reversed upon pine pollen treatment, which may account for its inhibitory effect on nonenzymatic glycation (NEG in vivo. Our finding presents pine pollen as an attractive agent with potential to retard aging and attenuate age-related diseases in humans.

  12. Assembly of infectious HIV-1 in human epithelial and T-lymphoblastic cell lines.

    Science.gov (United States)

    Grigorov, Boyan; Arcanger, Fabienne; Roingeard, Philippe; Darlix, Jean-Luc; Muriaux, Delphine

    2006-06-16

    The canonical view of the ultimate steps of HIV-1 replication is that virus assembly and budding are taking place at the plasma membrane of infected cells. Surprisingly, recent studies revealed that these steps also occur on endosomal membranes in the interior of infected cells, such as macrophages. This prompted us to revisit the site of HIV-1 assembly in human epithelial-like cells and in infected human T-lymphoblastic cells. To address this question, we investigated the intracellular location of the major viral structural components of HIV-1, namely Gag, Env and the genomic RNA. Using a sub-cellular fractionation method, as well as immuno-confocal and electron microscopy, we show that Gag, the Env glycoproteins and the genomic RNA accumulate in late endosomes that contain infectious HIV-1 particles. In epithelial-like 293T cells, HIV-1 assembles and buds both at the plasma membrane and in endosomes, while in chronically infected human T lymphocytes, viral assembly mostly occurs within the cell where large amounts of infectious virions accumulate in endosomal compartments. In addition, HIV-1 release could be enhanced by ionomycin, a drug stimulating calcium-dependent exocytosis. These results favour the view that newly made Gag molecules associate with the genomic RNA in the cytosol, then viral core complexes can be targeted to late endosomes together with Env, where infectious HIV-1 are made and subsequently released by exocytosis.

  13. Tocotrienol-Rich Fraction Prevents Cell Cycle Arrest and Elongates Telomere Length in Senescent Human Diploid Fibroblasts

    Directory of Open Access Journals (Sweden)

    Suzana Makpol

    2011-01-01

    Full Text Available This study determined the molecular mechanisms of tocotrienol-rich fraction (TRF in preventing cellular senescence of human diploid fibroblasts (HDFs. Primary culture of HDFs at various passages were incubated with 0.5 mg/mL TRF for 24 h. Telomere shortening with decreased telomerase activity was observed in senescent HDFs while the levels of damaged DNA and number of cells in G0/G1 phase were increased and S phase cells were decreased. Incubation with TRF reversed the morphology of senescent HDFs to resemble that of young cells with decreased activity of SA-β-gal, damaged DNA, and cells in G0/G1 phase while cells in the S phase were increased. Elongated telomere length and restoration of telomerase activity were observed in TRF-treated senescent HDFs. These findings confirmed the ability of tocotrienol-rich fraction in preventing HDFs cellular ageing by restoring telomere length and telomerase activity, reducing damaged DNA, and reversing cell cycle arrest associated with senescence.

  14. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  15. Cytotoxic and apoptotic effects of prenylflavonoid artonin B in human acute lymphoblastic leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Chun-chung LEE; Chun-nan LIN; Guey-mei JOW

    2006-01-01

    Aim: To investigate the anticancer effects and molecular mechanism of artonin B on the human acute lymphoblastic leukemia CCRF-CEM cells compared with other prenylflavonoid compounds. Methods: The effects of four prenylflavonoids on the growth of CCRF-CEM and HaCa cells were studied by 3-(4,5)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Apoptosis were detected through Hoechst 33258 staining. The effect of artonin B on the cell cycle of CCRF-CEM cells were studied by propidium iodide method. The change in mitochondrial membrane potential was detected by rohdamine 123 staining. The cytochrome c release and caspase 3 activity were checked by immunoassay kits, respectively. The expression of Bcl-2 family proteins was detected by Western blot. Results: Our data revealed that artonin B strongly induced human CCRF-CEM leukemia cell death in a dose- and time-dependent manner by MTT assay, but not on normal epithelia cells (HaCa cells). Artonin B-induced cell death was considered to be apoptotic by observing the typical apoptotic morphological change by Hoechst 33258 staining. The induction of human CCRF-CEM leukemia cancer cell death was caused by an induction of apoptosis through mitochondrial membrane potential change, cytochrome c release, sub-G1 proportion increase, downregulation of Bcl-2 expression, upregulation of Bax and Bak expression and activation of caspase 3 pathways. Conclusion: These results clearly demonstrated that artonin B is able to inhibit proliferation by induction of hypoploid cells and cell apoptosis. Moreover, the anticancer effects of artonin B were related to mitochondrial pathway and caspase 3 activation in human CCRF-CEM leukemia cells.

  16. Characterization of a TK6-Bcl-xL gly-159-ala Human Lymphoblast Clone

    Energy Technology Data Exchange (ETDEWEB)

    Chyall, L.: Gauny, S.; Kronenberg, A.

    2006-01-01

    TK6 cells are a well-characterized human B-lymphoblast cell line derived from WIL-2 cells. A derivative of the TK6 cell line that was stably transfected to express a mutated form of the anti-apoptotic protein Bcl-xL (TK6-Bcl-xL gly-159- ala clone #38) is compared with the parent cell line. Four parameters were evaluated for each cell line: growth under normal conditions, plating efficiency, and frequency of spontaneous mutation to 6‑thioguanine resistance (hypoxanthine phosphoribosyl transferase locus) or trifluorothymidine resistance (thymidine kinase locus). We conclude that the mutated Bcl-xL protein did not affect growth under normal conditions, plating efficiency or spontaneous mutation frequencies at the thymidine kinase (TK) locus. Results at the hypoxanthine phosphoribosyl transferase (HPRT) locus were inconclusive. A mutant fraction for TK6‑Bcl-xL gly-159-ala clone #38 cells exposed to 150cGy of 160kVp x-rays was also calculated. Exposure to x-irradiation increased the mutant fraction of TK6‑Bcl-xL gly-159-ala clone #38 cells.

  17. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

    Science.gov (United States)

    Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

    2014-01-01

    The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

  18. Diphtheria toxin resistance in human lymphocytes and lymphoblasts in the in vivo somatic cell mutation test

    Energy Technology Data Exchange (ETDEWEB)

    Tomkins, D.J.; Wei, L.; Laurie, K.E.

    1985-01-01

    It has been shown that circulating peripheral blood lymphocytes can be used for the enumeration of 6-thioguanine-resistant cells that presumably arise by mutation in vivo. This somatic cell mutation test has been studied in lymphocytes from human populations exposed to known mutagens and/or carcinogens. The sensitivity of the test could be further enhanced by including other gene markers, since there is evidence for locus-specific differences in response to mutagens. Resistance to diphtheria toxin (Dip/sup r/) seemed like a potential marker to incorporate into the test because the mutation acts codominantly, can readily be selected in human diploid fibroblasts and Chinese hamster cells with no evidence for cell density or cross-feeding effects, and can be assayed for in nondividing cells by measuring protein synthesis inhibition. Blood samples were collected from seven individuals, and fresh, cryopreserved, or Epstein-Barr virus (EBV)-transformed lymphocytes were tested for continued DNA synthesis (TH-thymidine, autoradiography) or protein synthesis (TVS-methionine, scintillation counting). Both fresh and cryopreserved lymphocytes, stimulated to divide with phytohemagglutinin (PHA), continued to synthesize DNA in the presence of high doses of diphtheria toxin (DT). Similarly, both dividing (PHA-stimulated) and nondividing fresh lymphocytes carried on significant levels of protein synthesis even 68 hr after exposure to 100 flocculating units (LF)/ml DT. The results suggest that human T and B lymphocytes may not be as sensitive to DT protein synthesis inhibition as human fibroblast and Chinese hamster cells. For this reason, Dip/sup r/ may not be a suitable marker for the somatic cell mutation test.

  19. Selecting Schizosaccharomyces pombe diploids

    DEFF Research Database (Denmark)

    Ekwall, Karl; Thon, Genevieve

    2017-01-01

    .g., for genetic complementation tests), and in these cases mating an h− strain with an h90 mat2-Pi-102 strain can be used to prevent sporulation. When ade6-M210/ade6-M216 mutations impact on, or show synthetic interactions with, the gene of interest, two different auxotrophic markers can be used to select......Here we describe procedures for the selection of diploid Schizosaccharomyces pombe. ade6-M210/ade6-M216 heteroallelic complementation is widely used to select for Ade+ diploids. Such diploids will readily sporulate when starved of nitrogen. For some investigations, stable diploids are preferable (e...

  20. Age dependency of the metabolic conversion of polyamines into amino acids in IMR-90 human embryonic lung diploid fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Chen, K.Y.; Chang, Z.

    1986-07-01

    When radioactive polyamines (putrescine or spermidine) were incubated with mammalian cells in tissue culture, the radioactivity was incorporated into cellular proteins via two different metabolic pathways; one is metabolic labeling of an 18,000-dalton protein via hypusine formation, and the other is general protein synthesis employing radioactive amino acids derived from biodegradation of polyamines via GABA shunt and Krebs cycle. Aminoguanidine, a potent inhibitor of diamine oxidase, blocked the metabolic conversion of polyamines to amino acids but had no effect on the metabolic labeling of the 18,000-dalton protein. The authors have investigated these two polyamine-associated biochemical events in IMR-90 human diploid fibroblasts as a function of their population doubling level (PDL). They found that (1) the metabolic labeling of the 18,000-dalton protein was about two-fold greater in young cells (PDL = 22) than that in old cells (PDL = 48), and (2) the metabolic labeling of other cellular proteins, employing amino acids derived from putrescine via polyamine catabolic pathway, was more than six-fold greater in the old cells (PDL = 48) than in the young cells (PDL = 22). Since the rate of protein synthesis was about 1.4-fold higher in the young cells as compared to the old cells, their data indicated that the activity of catabolic conversion of putrescine (or spermidine) to amino acids in old IMR-90 cells was about eight-fold greater than that in young cells. This remarkable increase of polyamine catabolism and the slight decrease of metabolic labeling of the 18,000-dalton protein were also observed in cell strains derived from patients with premature aging disease.

  1. Dramatic attenuation of hypusine formation on eukaryotic initiation factor 5A during senescence of IMR-90 human diploid fibroblasts.

    Science.gov (United States)

    Chen, Z P; Chen, K Y

    1997-03-01

    Deoxyhypusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (elF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on elF-5A. Hypusine formation is one of the most specific polyamine-dependent biochemical events in eukaryotic cells. Although changes in polyamine metabolism have been demonstrated in human diploid fibroblasts during senescence (Chen and Chang, 1986, J. Cell. Physiol., 128:27-32.), it is unclear whether or not polyamine-dependent hypusine formation itself is an age-dependent biochemical event. In the present study, hypusine-forming activity was measured by a radiolabeling assay in cells whose polyamines have been depleted by prior treatment of alpha-difluoromethyl ornithine (DFMO). In addition, an in vitro cross-labeling assay was developed for simultaneous measurement of the deoxyhypusine synthase activity and protein substrate (elF-5A precursor) amount. We showed that the hypusine-forming activity in low-passage presenescent IMR-90 cells [population doubling level (PDL) = 15-23, termed young cells] was prominently induced by serum whereas little or no hypusine-forming activity could be detected in late-passage senescent cells (PDL = 46-54, termed old cells). The striking difference in hypusine-forming activity between young and old cells was due to changes in both deoxyhypusine synthase activity and elF-5A precursor amount in IMR-90 cells during senescence. However, Northern blot analysis showed no significant difference in the elF-5A messenger RNA (mRNA) between young and old cells, suggesting that the age-dependent attenuation of elF-5A precursor protein may be regulated at either translational or post-translational level.

  2. SLAM family predicting the initiation potential of human acute lymphoblastic leukemia in NOD/SCID mice

    Institute of Scientific and Technical Information of China (English)

    WANG Na; ZHOU Jian-feng; HUANG Liang; XIAO Fei; LIU Jin-ping; WANG Di; GENG Zhe; WANG Jin; MA Shu-yan; SHU Li-li; CHEN Tai-ping

    2011-01-01

    Background The SLAM family recently has been reported to show an important biological role in lymphocyte development and immunological function, and it is efficient to highly purify hematopoietic stem cells using a simple combination of SLAM family members. To elucidate the presence of this family on acute lymphoblastic leukemia (ALL),as well as its relationship with the leukemia-initiating potential, we analyzed the expression pattern of this family members on human ALL progenitor cells, combined with serial xenotransplantation assay.Methods Expression analysis was carried out by flow cytometry. We combined the expression pattern of human CD150,CD244 and CD48 with serial xenotransplantation of B-ALL progenitor cells to indicate their relationship.Results CD48 and CD244 were expressed on most B-ALL progenitor cells, the percentage being (93.08±6.46)% and (63.37±29.31)%, respectively. Interestingly, the proportion of CD150+ cells declined obviously in engrafted cases ((24.94±7.32)%) compared with non-engrafted cases ((77.54±5.93)%, P <0.01), which indicated that only blast cells with low percentage of CD150+ population were able to reconstitute leukemia into primary, secondary and tertiary NOD/SCID mice.Conclusions SLAM family members are present on B-ALL progenitor cells and the leukemia-initiating potential of leukemic blasts is correlated negatively with the proportion of CD150+ cells, the percentage of which can serve as a useful predictor for engraftment success of B-ALL to immune deficient mice.

  3. Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Candelario, Jose; Borrego, Stacey [Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Reddy, Sita, E-mail: sitaredd@usc.edu [Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Comai, Lucio, E-mail: comai@usc.edu [Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States)

    2011-02-01

    Lamin A is a component of the nuclear lamina that plays a major role in the structural organization and function of the nucleus. Lamin A is synthesized as a prelamin A precursor which undergoes four sequential post-translational modifications to generate mature lamin A. Significantly, a large number of point mutations in the LMNA gene cause a range of distinct human disorders collectively known as laminopathies. The mechanisms by which mutations in lamin A affect cell function and cause disease are unclear. Interestingly, recent studies have suggested that alterations in the normal lamin A pathway can contribute to cellular dysfunction. Specifically, we and others have shown, at the cellular level, that in the absence of mutations or altered splicing events, increased expression of wild-type prelamin A results in a growth defective phenotype that resembles that of cells expressing the mutant form of lamin A, termed progerin, associated with Hutchinson-Gilford Progeria syndrome (HGPS). Remarkably, the phenotypes of cells expressing elevated levels of wild-type prelamin A can be reversed by either treatment with farnesyltransferase inhibitors or overexpression of ZMPSTE24, a critical prelamin A processing enzyme, suggesting that minor increases in the steady-state levels of one or more prelamin A intermediates is sufficient to induce cellular toxicity. Here, to investigate the molecular basis of the lamin A pathway toxicity, we characterized the phenotypic changes occurring in cells expressing distinct prelamin A variants mimicking specific prelamin A processing intermediates. This analysis demonstrates that distinct prelamin A variants differentially affect cell growth, nuclear membrane morphology, nuclear distribution of lamin A and the fundamental process of transcription. Expression of prelamin A variants that are constitutively farnesylated induced the formation of lamin A aggregates and dramatic changes in nuclear membrane morphology, which led to reduced

  4. Epigenetic inactivation of Notch-Hes pathway in human B-cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Shao-Qing Kuang

    Full Text Available The Notch pathway can have both oncogenic and tumor suppressor roles, depending on cell context. For example, Notch signaling promotes T cell differentiation and is leukemogenic in T cells, whereas it inhibits early B cell differentiation and acts as a tumor suppressor in B cell leukemia where it induces growth arrest and apoptosis. The regulatory mechanisms that contribute to these opposing roles are not understood. Aberrant promoter DNA methylation and histone modifications are associated with silencing of tumor suppressor genes and have been implicated in leukemogenesis. Using methylated CpG island amplification (MCA/DNA promoter microarray, we identified Notch3 and Hes5 as hypermethylated in human B cell acute lymphoblastic leukemia (ALL. We investigated the methylation status of other Notch pathway genes by bisulfite pyrosequencing. Notch3, JAG1, Hes2, Hes4 and Hes5 were frequently hypermethylated in B leukemia cell lines and primary B-ALL, in contrast to T-ALL cell lines and patient samples. Aberrant methylation of Notch3 and Hes5 in B-ALL was associated with gene silencing and was accompanied by decrease of H3K4 trimethylation and H3K9 acetylation and gain of H3K9 trimethylation and H3K27 trimethylation. 5-aza-2'-deoxycytidine treatment restored Hes5 expression and decreased promoter hypermethylation in most leukemia cell lines and primary B-ALL samples. Restoration of Hes5 expression by lentiviral transduction resulted in growth arrest and apoptosis in Hes5 negative B-ALL cells but not in Hes5 expressing T-ALL cells. These data suggest that epigenetic modifications are implicated in silencing of tumor suppressor of Notch/Hes pathway in B-ALL.

  5. Diploid versus Haploid Organisms

    Science.gov (United States)

    Ticona, Armando; de Oliveira, Paulo Murilo C.

    Using a bit string model, we show that asexual reproduction for diploids is more efficient than for haploids: it improves genetic material producing new individuals with less deleterious mutations. We also see that in a system where competition is present, diploids dominate, even though we consider some dominant loci.

  6. 99Tcm-N(NOEt2 Uptake Kinetics Difference among KMB17 Human Embryonic Lung Diploid Fibroblast and Different Human Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wei JIA

    2010-04-01

    Full Text Available Background and objective PET/CT imaging is expensive, so searching the tumor imaging agent for SPECT/CT is necessary. 99Tcm-N(NOEt2 [bis (N-ethoxy-N-ethyl dithiocarbamato nitrido99Tcm (V] can be uptaken by lung cancer cells and other cells alike. The aim of this study is to evaluate the distinctive value in lung tumor with 99Tcm-N(NOEt2, the difference in its uptake kinetics in human embryonic lung diploid fibroblasts KMB17 and several kinds of lung cancer cells lines. Methods Firstly, six different cell culture medium which contained YTMLC Gejiu human lung squamous carcinoma cell, SPC-A1 human lung adenocarcinoma cell, AGZY low metastatic human lung adenocarcinoma, 973 high metastatic human lung adenocarcinoma cell, GLC-82 Gejiu human lung adenocarcinoma cell, and KMB17 human embryonic lung diploid fibroblast, respectively with equal cell density of 1×106/mL and the same volume were prepared; secondly, the same radioactive dose of 99Tcm-N(NOEt2 was added into each sample and then 300 μL mixed sample was taken out respectively and cultured in 37 oC culture box; Finally, 5 min, 15 min, 30 min, 45 min, 60 min, 75 min, 90 min after cultivation, centrifuged each cultured sample and determined the intracellular radiocounts of each sample, calculated each cell sample’s uptake rate of 99Tcm-N(NOEt2 at different time. Results Statistical difference was found among six cell samples, and the uptake rate sequence from high to low is 973 and SPC-A1>YTMLC>GLC-82>AGZY>KMB17 respectively; furthermore, 30 min-45 min after culture, the uptake rate reached stability, and the 45 min uptake rate of each sample was higher than its 96.7% uptake peak. Conclusion Based on the results above mentioned, it is supposed that there are discriminative clinical value when using 99Tcm-N(NOEt2 as a tumor targeting imaging agent, and 30 min or so after injection may be the best imaging time in the early imaging stage.

  7. Efficient retrovirus-mediated transfer and expression of a human adenosine deaminase gene in diploid skin fibroblasts from an adenosine deaminase-deficient human

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, T.D.; Hock, R.A.; Osborne, W.R.A.; Miller, A.D.

    1987-02-01

    Skin fibroblasts might be considered suitable recipients for therapeutic genes to cure several human genetic diseases; however, these cells are resistant to gene transfer by most methods. The authors studied the ability of retroviral vectors to transfer genes into normal human diploid skin fibroblasts. Retroviruses carrying genes for neomycin or hygromycin B resistance conferred drug resistance to greater than 50% of the human fibroblasts after a single exposure to virus-containing medium. This represents at least a 500-fold increase in efficiency over other methods. Transfer was achieved in the absence of helper virus by using amphotropic retrovirus-packaging cells. A retrovirus vector containing a human adenosine deaminase (ADA) cDNA was constructed and used to infect ADA/sup -/ fibroblasts from a patient with ADA deficiency. The infected cells produced 12-fold more ADA enzyme than fibroblasts from normal individuals and were able to rapidly metabolize exogenous deoxyadenosine and adenosine, metabolites that accumulate in plasma in ADA-deficient patients and are responsible for the severe combined immunodeficiency in these patients. These experiments indicate the potential of retrovirus-mediated gene transfer into human fibroblasts for gene therapy.

  8. Identification of lipid profile on γ-irradiated primary cultured human diploid fibroblasts by UPLC-ESI-QTOF-MS

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Kyeong; Yun, Hyun Jin; Kim, Sun Young; Kim, So Ra; Kim, Eun Ju; Kang, Chang Mo [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Hwang, Geum Sook [Integrated Metabolomics Research Group, Korea Basic Science Institute, Sejong (Korea, Republic of)

    2013-11-15

    The study of biomarkers in normal-tissue radiobiology is of great importance to people subjected to non-destructive testing, to nuclear power industry, and to radiological terrorism. Cytogenetics has remained the 'gold standard' for the detection of chromosomal changes, but this method is cumbersome and time consuming. Therefore, it is necessary to establish a rapid, high-throughput biological monitoring protocol to determine the exposure radiation dose in order to rapidly triage mass casualties. Metabolomics studies is an effective platform for identification and quantification of the complete set of metabolites in a biological system, and it has been successfully provides important insights into physiological and disease states and facilitate in depth understanding of underlying biochemical pathways. Radiation metabolomics has been used to identify radiation effects at the metabolite levels in cells and in urine or serum collected from laboratory animals such as mouse, rat and monkey. Recently, a few radiation metabolomics studies showed that multiple metabolites related to the purine, inositol or pyrimidine metabolism, fatty acid biosynthesis and glycolysis/gluconeogenesis could be potential minimal-invasive markers for radiation exposure. However, there is little consistency in these studies due to differences in analyzed sample (cells, urine, serum), animal models (mouse, rat and monkey). Furthermore, the biological effects of ionizing radiation (IR) were differently regulated in the different absorbed doses, dose-rates and type of IR. Thus, it is necessary to explore the entire biosphere profiling of metabolic markers to make reasonable biological explanation under radiation exposure. We hypothesized that the variations in lipid expression in IR-induced cells would result in a unique lipid profile in human diploid fibroblasts (HDF), which can be detected with the targeted and quantitative metabolomics approach. Irradiated HDF cells showed the dose

  9. Studying the cytotoxicity and oxidative stress induced by two kinds of bentonite particles on human B lymphoblast cells in vitro.

    Science.gov (United States)

    Zhang, Meibian; Lu, Yezhen; Li, Xiaoxue; Chen, Qing; Lu, Longxi; Xing, Mingluan; Zou, Hua; He, Jiliang

    2010-02-12

    The aim of the present study was to evaluate the cytotoxicity and oxidative stress induced by native and active bentonite particles (BPs) on human B lymphoblast cells using seven assays. Our results showed that the order of cytotoxicity was: active BPs>native BPs>quartz particles (DQ-12)>gypsum, according to the IC50 values in CCK-8 assay and neutral red uptake (NRU) assay. The lactate dehydrogenase (LDH) leakage, the proportions of early apoptotic cells, the reactive oxygen species (ROS) generation, the superoxide dismutase (SOD) inhibition and the malondialdehyde (MDA) release in the native and active BPs groups were significantly higher than those in the gypsum and DQ-12 groups (Pstress induced by active BPs was significantly higher than that induced by native BPs (Pstress on human B lymphoblast cells in vitro. The cytotoxic difference between active BPs and native BPs may be associated with the adsorption capacity of BPs and oxidative stress induced by BPs to a certain extent. The insoluble particle fractions may play a main role in the cytotoxic effects and oxidative stress induced by BPs.

  10. The biogenesis of the MHC class II compartment in human I-cell disease B lymphoblasts

    OpenAIRE

    1996-01-01

    The localization and intracellular transport of major histocompatibility complex (MHC) class II molecules nd lysosomal hydrolases were studied in I-Cell Disease (ICD) B lymphoblasts, which possess a mannose 6-phosphate (Man-6-P)-independent targeting pathway for lysosomal enzymes. In the trans-Golgi network (TGN), MHC class II- invariant chain complexes colocalized with the lysosomal hydrolase cathepsin D in buds and vesicles that lacked markers of clathrin-coated vesicle-mediated transport. ...

  11. Mouse Lymphoblastic Leukemias Induced by Aberrant Prdm14 Expression Demonstrate Widespread Copy Number Alterations Also Found in Human ALL

    Directory of Open Access Journals (Sweden)

    Stephen J. Simko

    2012-10-01

    Full Text Available Aberrant expression and activation of oncogenes in somatic cells has been associated with cancer initiation. Required for reacquisition of pluripotency in the developing germ cell, PRDM14 initiates lymphoblastic leukemia when misexpressed in murine bone marrow. Activation of pluripotency in somatic cells can lead to aneuploidy and copy number alterations during iPS cell generation, and we hypothesized that PRDM14-induced lymphoblastic leukemias would demonstrate significant chromosomal damage. High-resolution oligo array comparative genomic hybridization demonstrated infrequent aneuploidy but frequent amplification and deletion, with amplifications occurring in a 5:1 ratio with deletions. Many deletions (i.e., Cdkn2a, Ebf1, Pax5, Ikzf1 involved B-cell development genes and tumor suppressor genes, recapitulating deletions occurring in human leukemia. Pathways opposing senescence were frequently deactivated via Cdkn2a deletion or Tbx2 amplification, with corollary gene expression. Additionally, gene expression studies of abnormal pre-leukemic B-precursors showed downregulation of genes involved in chromosomal stability (i.e., Xrcc6 and failure to upregulate DNA repair pathways. We propose a model of leukemogenesis, triggered by pluripotency genes like Prdm14, which involves ongoing DNA damage and failure to activate non-homologous end-joining secondary to aberrant gene expression.

  12. Lack of dependence on p53 for DNA double strand break repair of episomal vectors in human lymphoblasts

    Science.gov (United States)

    Kohli, M.; Jorgensen, T. J.

    1999-01-01

    The p53 tumor suppressor gene has been shown to be involved in a variety of repair processes, and recent findings have suggested that p53 may be involved in DNA double strand break repair in irradiated cells. The role of p53 in DNA double strand break repair, however, has not been fully investigated. In this study, we have constructed a novel Epstein-Barr virus (EBV)-based shuttle vector, designated as pZEBNA, to explore the influence of p53 on DNA strand break repair in human lymphoblasts, since EBV-based vectors do not inactivate the p53 pathway. We have compared plasmid survival of irradiated, restriction enzyme linearized, and calf intestinal alkaline phosphatase (CIP)-treated pZEBNA with a Simian virus 40 (SV40)-based shuttle vector, pZ189, in TK6 (wild-type p53) and WTK1 (mutant p53) lymphoblasts and determined that p53 does not modulate DNA double strand break repair in these cell lines. Copyright 1999 Academic Press.

  13. Alkaloids from the poisonous plant Ipomoea carnea: effects on intracellular lysosomal glycosidase activities in human lymphoblast cultures.

    Science.gov (United States)

    Ikeda, Kyoko; Kato, Atsushi; Adachi, Isao; Haraguchi, Mitsue; Asano, Naoki

    2003-12-17

    There is natural intoxication of livestock by the ingestion of Ipomoea carnea (Convolvulaceae) in Brazil and other parts of the world. The alkaloidal glycosidase inhibitors swainsonine, 2-epi-lentiginosine, and calystegines B(1), B(2), B(3), and C(1) have been identified as constituents of this plant. Swainsonine is a potent inhibitor of rat lysosomal alpha-mannosidase, with an IC(50) value of 0.02 microM, whereas calystegines B(1), B(2), and C(1) are potent inhibitors of rat lysosomal beta-glucosidase, with IC(50) values of 2.1, 0.75, and 0.84 microM, respectively. The action of swainsonine results in a lysosomal storage disorder that closely mimics alpha-mannosidosis in humans. To determine whether the toxicity of I. carnea to livestock is due to purely swainsonine or due to a combination of effects by swainsonine and calystegines, intracellular lysosomal glycosidase activities in normal human lymphoblasts grown with inhibitors in the medium were examined. Incubation of lymphoblasts with 0.1 microM swainsonine for 3 days resulted in approximately 60% reduction of alpha-mannosidase activity. On the other hand, calystegines B(2) and C(1) showed no inhibition of beta-glucosidase up to 1 mM; instead inclusion of calystegines B(2) and C(1) at 100 microM in the culture medium increased its activity by 1.5- and 1.6-fold, respectively. Calystegines B(2) and C(1) seem to act as chemical chaperones, enhancing correct folding of the enzyme and enabling smooth trafficking to the lysosome. The lysosomal beta-glucosidase inhibitory calystegines seem to have little risk of inducing intoxication of livestock.

  14. Dual pathways for ribonucleic acid turnover in WI-38 but not in I-cell human diploid fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Sameshima, M.; Liebhaber, S.A.; Schlessinger, D.

    1981-01-01

    The turnover rates of /sup 3/H-labeled 18S ribosomal ribonucleic acid (RNA), 28S ribsomal RNA, transfer RNA, and total cytoplasmic RNA were very similar in growing WI-38 diploid fibroblasts. The rate of turnover was at least twofold greater when cell growth stopped due to cell confluence, /sup 3/H irradiation, or treatment with 20 mM NaN/sub 3/ or 2 mM NaF. In contrast, the rate of total /sup 3/H-protein turnover was the same in growing and nongrowing cells. Both RNA and protein turnovers were accelerated at least twofold in WI-38 cells deprived of serum, and this increase in turnover was inhibited by NH/sub 4/Cl. These results are consistent with two pathways for RNA turnover, oe of them being nonlysosomal and the other being lyosome mediated (NH/sub 4/Cl sensitive), as has been suggested for protein turnover. Also consistent with the notion of two pathways for RNA turnover were findings with I-cells, which are deficient for many lysosomal enzymes, and in which all RNA turnover were nonlysosomal (NH/sub 4/Cl resistant).

  15. Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyoung Jun; Lee, Yura [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of); Kim, Soon Ae [Department of Pharmacology, School of Medicine, Daejeon 34824 (Korea, Republic of); Kim, Jiyeon, E-mail: yeon@eulji.ac.kr [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of)

    2016-04-22

    Of the hematological disorders typified by poor prognoses and survival rates, T-cell acute lymphoblastic leukemia (T-ALL) is one of the most commonly diagnosed. Despite the development of new therapeutic agents, the treatment options for this cancer remain limited. In this manuscript, we investigated the anti-proliferative effects of plumbagin, mediated by the activation of mitogen-activated protein kinase (MAPK) pathways, and inhibition of NF-κB signaling; the human T-ALL MOLT-4 cell line was used as our experimental system. Plumbagin is a natural, plant derived compound, which exerts an anti-proliferative activity against many types of human cancer. Our experiments confirm that plumbagin induces a caspase-dependent apoptosis of MOLT-4 cells, with no significant cytotoxicity seen for normal peripheral blood mononuclear cells (PBMCs). Plumbagin also inhibited LPS-induced phosphorylation of p65, and the transcription of NF-κB target genes. Our results now show that plumbagin is a potent inhibitor of the NF-κB signaling pathway, and suppressor of T-ALL cell proliferation. - Highlights: • Plumbagin induces caspase-dependent apoptosis in T-ALL MOLT-4 cells. • Plumbagin activates phosphorylation of stress-activated protein kinase (SAPK) JNK and p38. • Plumbagin inhibits LPS-mediated NF-κB signaling cascade. • Plumbagin inhibits LPS-mediated transcriptional activity of pro-inflammatory cytokines.

  16. Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hiroto [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Wilson Xu, C. [Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States); Naito, Motohiko [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Nishida, Hiroko [Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Okamoto, Toshihiro; Ghani, Farhana Ishrat; Iwata, Satoshi [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Inukai, Takeshi; Sugita, Kanji [Department of Pediatrics, School of Medicine, University of Yamanashi, Yamanashi (Japan); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States)

    2011-05-27

    Highlights: {yields} We performed more detailed analysis of CD9 function for CSC properties in B-ALL. {yields} Leukemogenic fusion/Src family proteins were markedly regulated in the CD9{sup +} cells. {yields} Proliferation of B-ALL cells was inhibited by anti-CD9 monoclonal antibody. {yields} Knockdown of CD9 by RNAi remarkably reduced the leukemogenic potential. {yields} CD9-knockdown affected the expression and phosphorylation of Src family and USP22. -- Abstract: Although the prognosis of acute lymphoblastic leukemia (ALL) has improved considerably in recent years, some of the cases still exhibit therapy-resistant. We have previously reported that CD9 was expressed heterogeneously in B-ALL cell lines and CD9{sup +} cells exhibited an asymmetric cell division with greater tumorigenic potential than CD9{sup -} cells. CD9{sup +} cells were also serially transplantable in immunodeficient mice, indicating that CD9{sup +} cell possess self-renewal capacity. In the current study, we performed more detailed analysis of CD9 function for the cancer stem cell (CSC) properties. In patient sample, CD9 was expressed in the most cases of B-ALL cells with significant correlation of CD34-expression. Gene expression analysis revealed that leukemogenic fusion proteins and Src family proteins were significantly regulated in the CD9{sup +} population. Moreover, CD9{sup +} cells exhibited drug-resistance, but proliferation of bulk cells was inhibited by anti-CD9 monoclonal antibody. Knockdown of CD9 remarkably reduced the leukemogenic potential. Furthermore, gene ablation of CD9 affected the expression and tyrosine-phosphorylation of Src family proteins and reduced the expression of histone-deubiquitinase USP22. Taken together, our results suggest that CD9 links to several signaling pathways and epigenetic modification for regulating the CSC properties of B-ALL.

  17. Diphtheria Toxin/Human B-Cell Activating Factor Fusion Protein Kills Human Acute Lymphoblastic Leukemia BALL-1 Cells: An Experimental Study

    Institute of Scientific and Technical Information of China (English)

    Xin-pu Gao; Zheng-min Liu; Yu-lian Jiao; Bin Cui; Yue-ting Zhu; Jie Zhang; Lai-cheng Wang; Yue-ran Zhao

    2012-01-01

    Objective:This study aimed to express a fusion protein of diphtheria toxin and human B ceil-activating factor (DT388sBAFF) in Escherichia coli (E.coli) and investigate its activity in human B-lineage acute lymphoblastic leukemia 1 cells (BALL-1).Methods:A fragment of DT388sBAFF fusion gene was separated from plasmid pUC57-DT388sBAFF digested with Nde Ⅰ and Xho Ⅰ,and inserted into the expression vector pcold Ⅱ digested with the same enzymes.Recombinants were screened by the colony polymerase chain reaction (PCR) and restriction map.The recombinant expression vector was transformed into BL21 and its expression was induced by isopropyl β-D-1-thiogalactopyranoside (IPTG).The recombinant protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot,and then purified by Ni2+-NTA affinity chromatography.The expression level of B cell-activating factor receptor (BAFF-R) on BALL-1 cells was assessed by real-time PCR.The receptor binding capacity of recombinant protein was determined by cell fluorescent assay.The specific cytotoxicity of recombinant protein on BALL-1 cells was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay.Results:The expression level of recombinant protein was 50% of total bacterial proteins in E.coli,and the recombinant protein could bind to BAFF-R-positive BALL-1 cells and thereby produce a cytotoxic effect on the cells.Conclusion:The fusion protein expression vector DT388sBAFF was successfully constructed and the recombinant protein with selective cytotoxicity against BALL-1 cells was obtained,providing foundation for further study of the therapy of human B-lineage acute lymphoblastic leukemia.

  18. Treatment of human pre-B acute lymphoblastic leukemia with the Aurora kinase inhibitor PHA-739358 (Danusertib

    Directory of Open Access Journals (Sweden)

    Fei Fei

    2012-06-01

    Full Text Available Abstract Background Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemias (Ph-positive ALL with clinically approved inhibitors of the Bcr/Abl tyrosine kinase frequently results in the emergence of a leukemic clone carrying the T315I mutation in Bcr/Abl, which confers resistance to these drugs. PHA-739358, an Aurora kinase inhibitor, was reported to inhibit the Bcr/Abl T315I mutant in CML cells but no preclinical studies have examined this in detail in human ALL. Results We compared the sensitivity of human Bcr/Abl T315I, Bcr/Abl wild type and non-Bcr/Abl ALL cells to this drug. PHA-739358 inhibited proliferation and induced apoptosis independently of Bcr/Abl, the T315I mutation, or presence of the tumor suppressor p53, but the degree of effectiveness varied between different ALL samples. Since short-term treatment with a single dose of drug only transiently inhibited proliferation, we tested combination treatments of PHA-739358 with the farnesyltransferase inhibitor Lonafarnib, with vincristine and with dasatinib. All combinations reduced viability and cell numbers compared to treatment with a single drug. Clonogenic assays showed that 25 nM PHA-739358 significantly reduced the colony growth potential of Ph-positive ALL cells, and combined treatment with a second drug abrogated colony growth in this assay. PHA-739358 further effectively blocked Bcr/Abl tyrosine kinase activity and Aurora kinase B in vivo, and mice transplanted with human Bcr/Abl T315I ALL cells treated with a 3x 7-day cycle of PHA-739358 as mono-treatment had significantly longer survival. Conclusions PHA-739358 represents an alternative drug for the treatment of both Ph-positive and negative ALL, although combined treatment with a second drug may be needed to eradicate the leukemic cells.

  19. Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction on antioxidant enzymes activity in cellular ageing of human diploid fibroblasts.

    Science.gov (United States)

    Makpol, Suzana; Yeoh, Thong Wei; Ruslam, Farah Adilah Che; Arifin, Khaizurin Tajul; Yusof, Yasmin Anum Mohd

    2013-08-16

    Human diploid fibroblasts (HDFs) undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular ageing. Even though beneficial effects of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction (TRF) have been reported, ongoing studies in relation to ageing is of interest to determine possible protective effects that may reverse the effect of ageing. The aim of this study was to evaluate the effect of P. betle, C. vulgaris and TRF in preventing cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.; catalase, superoxide dismutase (SOD) and glutathione peroxidase. Different passages of HDFs were treated with P. betle, C. vulgaris and TRF for 24 h prior to enzymes activity determination. Senescence-associated beta-galactosidase (SA β-gal) expression was assayed to validate cellular ageing. In cellular ageing of HDFs, catalase and glutathione peroxidase activities were reduced, but SOD activity was heightened during pre-senescence. P. betle exhibited the strongest antioxidant activity by reducing SA β-gal expression, catalase activities in all age groups, and SOD activity. TRF exhibited a strong antioxidant activity by reducing SA β-gal expression, and SOD activity in senescent HDFs. C. vulgaris extract managed to reduce SOD activity in senescent HDFs. P. betle, C. vulgaris, and TRF have the potential as anti-ageing entities which compensated the role of antioxidant enzymes in cellular ageing of HDFs.

  20. Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax in the Vaccine Adverse Event Reporting System (VAERS in the United States, 1990‒2015.

    Directory of Open Access Journals (Sweden)

    Pedro L Moro

    2016-07-01

    Full Text Available In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur, was licensed for use in the United States.To assess adverse events (AEs after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS, a spontaneous reporting surveillance system.We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990-July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness, and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS. Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB data mining was used to identify disproportional AE reporting after HDCV.VAERS received 1,611 reports after HDCV; 93 (5.8% were serious. Among all reports, the three most common AEs included pyrexia (18.2%, headache (17.9%, and nausea (16.5%. Among serious reports, four deaths appeared to be unrelated to vaccination.This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies.

  1. Comparative study of the immunogenicity in mice and monkeys of an inactivated CA16 vaccine made from a human diploid cell line.

    Science.gov (United States)

    Yang, Erxia; Cheng, Chen; Zhang, Ying; Wang, Jingjing; Che, Yanchun; Pu, Jing; Dong, Chenghong; Liu, Longding; He, Zhanlong; Lu, Shuaiyao; Zhao, Yuan; Jiang, Li; Liao, Yun; Shao, Congwen; Li, Qihan

    2014-01-01

    The coxsackie A16 virus (CA16), along with enterovirus 71 (EV71), is a primary pathogen that causes hand, foot, and mouth disease (HFMD). To control HFMD, CA16, and EV71 vaccines are needed. In this study, an experimental inactivated CA16 vaccine was prepared using human diploid cells, and the vaccine's immunogenicity was analyzed in mice and rhesus monkeys. The results showed that the neutralizing antibody was developed in a dose-dependent manner, and was sustained for 70 days with an average GMT (geometric mean titer) level of 80 to 90 in immunized mouse and for 56 days with GMT of higher than 300 in monkeys. The neutralizing antibody had a cross-neutralizing activity against different viral strains (genotype A and B), and the specific IFN-γ-secreting cell response was activated by these virus strains in an ELISPOT assay. This study provides evidence for the potential use of inactivated CA16 as a candidate for use in vaccines.

  2. Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax) in the Vaccine Adverse Event Reporting System (VAERS) in the United States, 1990‒2015

    Science.gov (United States)

    Moro, Pedro L.; Woo, Emily Jane; Paul, Wendy; Lewis, Paige; Petersen, Brett W.; Cano, Maria

    2016-01-01

    Background In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur), was licensed for use in the United States. Objective To assess adverse events (AEs) after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. Methods We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990–July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB) data mining was used to identify disproportional AE reporting after HDCV. Results VAERS received 1,611 reports after HDCV; 93 (5.8%) were serious. Among all reports, the three most common AEs included pyrexia (18.2%), headache (17.9%), and nausea (16.5%). Among serious reports, four deaths appeared to be unrelated to vaccination. Conclusions This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies. PMID:27410239

  3. Energy-dependent reduced drug binding as a mechanism of Vinca alkaloid resistance in human leukemic lymphoblasts.

    Science.gov (United States)

    Beck, W T; Cirtain, M C; Lefko, J L

    1983-11-01

    We studied the accumulation of [3H]vinblastine (VLB) by lines of CCRF-CEM cultured human leukemic lymphoblasts that were either sensitive or resistant to the drug. Neither cell line metabolized VLB, nor selectively retained any radioactive impurities. There was an apparent "instantaneous" accumulation of VLB by cells of both lines, resulting in cell to medium ratios greater than 1.0 within 1 sec after drug addition. Experiments between 0 and 60 sec revealed that the presumed undirectional initial rate of VLB accumulation by resistant cells, termed CEM/VLB100, was about one-half that of sensitive CEM cells. In experiments carried out over 60 min, the VLB-resistant cells accumulated considerably less [3H]VLB than did the sensitive cells. Drug accumulation by both cell lines was temperature-sensitive, since incubation of cells at 4 degrees resulted in only minimal uptake beyond that observed at zero time. CEM/VLB100 cells retained less drug than did CEM cells, apparently because of a larger fraction of readily releasable VLB compared with CEM cells. The accumulation of VLB by either cell line was related in part to cellular levels of ATP. Although depletion of ATP was associated with decreased accumulation of VLB by CEM cells, it was related to enhanced drug accumulation by CEM/VLB100 cells. Restoration of ATP levels to near control values by addition of glucose also had opposite effects on the two cell lines, causing further accumulation of VLB by the sensitive line but leading to apparent drug efflux from the resistant line. Potentially competing substrates (VM-26, colchicine, daunorubicin, and doxorubicin) failed to block this glucose-mediated release of VLB from the CEM/VLB100 cells. In experiments with energy-depleted CEM/VLB100 cells preloaded with VLB and then incubated in drug-free medium, initial drug loss was shown to be independent of cellular metabolism, being roughly the same for both metabolically intact and metabolically depleted cells. Glucose (energy

  4. In Vitro Cytotoxic Effects of Cuscuta chinensis Whole Extract on Human Acute Lymphoblastic Leukemia Cell Line

    Directory of Open Access Journals (Sweden)

    Fatemeh Zeraati

    2010-12-01

    Full Text Available Background: One of the major paths for drug development isthe study of bioactivities of natural products. Therefore, theaim of this study was to compare the cytotoxic effects ofaqueous extract of whole Cuscuta chinensis Lam., which is atraditional medicinal herb commonly used in Iran and otheroriental countries, on the human caucasian acute lymphoblasticleukemia (CCRF-CEM and another human lymphocyte,Jurkat (JM cell lines.Methods: In vitro cytotoxic screening with various concentrations(0, 0.1, 1, 10, 25 and 50 μg/ml of the extract wasperformed using microscope and methyl tetrazolium bromidetest (MTT.Results: The minimum effective concentration of the plantextract was 1 μg/ml, and increasing the dose to 10 μg/mlinduced increasingly stronger effects. The inhibitory concentration50% (IC50 of the extract against CCRF wasabout 3 μg/ml in 24 hours and 2.5 μg/ml in 48 hrs. In contrast,the extract did not have cytotoxic effect for the JMcells at these doses.Conclusion: The findings of the present study suggest that C.chinensis is toxic against CCRF-CEM and JM tumor cells.Whether or not such effects can be employed for the treatmentof such tumors must await future studies.Iran J Med Sci 2010; 35(4: 310-314.

  5. Origin of Cryptococcus neoformans var. neoformans Diploid Strains

    Science.gov (United States)

    Cogliati, Massimo; Esposto, Maria C.; Clarke, David L.; Wickes, Brian L.; Viviani, Maria A.

    2001-01-01

    The basidiomycetous yeast Cryptococcus neoformans is an important human fungal pathogen. Two varieties, C. neoformans var. neoformans and C. neoformans var. gattii, have been identified. Both are heterothallic with two mating types, MATa and MATα. Some rare isolates are self-fertile and are considered occasional diploid or aneuploid strains. In the present study, 133 isolates, mostly from Italian patients, were investigated to detect the presence of diploid strains in the Igiene Università Milano culture collection. All of the diploid isolates were further investigated by different methods to elucidate their origins. Forty-nine diploid strains were identified by flow cytometry. PCR fingerprinting using the (GACA)4 primer showed that the diploid state was associated with two specific genotypes identified as VN3 and VN4. Determination of mating type on V8 juice medium confirmed that the majority of the strains were sterile. PCR and dot blotting using the two pheromone genes (MFa and MFα) as probes identified 36 of the 49 diploid isolates as MATa/α. The results of pheromone gene sequencing showed that two allelic MFα genes exist and are distinct for serotypes A and D. In contrast, the MFa gene sequence was conserved in both serotype alleles. Amplification of serotype-specific STE20 alleles demonstrated that the diploid strains contained one mating locus inherited from a serotype A parent and one inherited from a serotype D parent. The present results suggest that diploid isolates may be common among the C. neoformans population and that in Italy and other European countries serotype A and D populations are not genetically isolated but are able to recombine by sexual reproduction. PMID:11682503

  6. Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line

    Directory of Open Access Journals (Sweden)

    Rahman HS

    2014-01-01

    Full Text Available Heshu Sulaiman Rahman,1–3 Abdullah Rasedee,1,2 Ahmad Bustamam Abdul,2,4 Nazariah Allaudin Zeenathul,1,2 Hemn Hassan Othman,1,3 Swee Keong Yeap,2 Chee Wun How,2 Wan Abd Ghani Wan Nor Hafiza4,51Faculty of Veterinary Medicine, 2Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia; 3Faculty of Veterinary Medicine, University of Sulaimanyah, Sulaimanyah City, Kurdistan Region, Northern Iraq; 4Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia; 5College of Medical Laboratory Technology, Institute for Medical Research, Kuala Lumpur, MalaysiaAbstract: This investigation evaluated the antileukemia properties of a zerumbone (ZER-loaded nanostructured lipid carrier (NLC prepared by hot high-pressure homogenization techniques in an acute human lymphoblastic leukemia (Jurkat cell line in vitro. The apoptogenic effect of the ZER-NLC on Jurkat cells was determined by fluorescent and electron microscopy, Annexin V-fluorescein isothiocyanate, Tdt-mediated dUTP nick-end labeling assay, cell cycle analysis, and caspase activity. An MTT (3-(4,5-dimethylthiazol-2-yl-2,5 diphenyltetrazolium bromide assay showed that ZER-NLC did not have adverse effects on normal human peripheral blood mononuclear cells. ZER-NLC arrested the Jurkat cells at G2/M phase with inactivation of cyclin B1 protein. The study also showed that the antiproliferative effect of ZER-NLC on Jurkat cells is through the intrinsic apoptotic pathway via activation of caspase-3 and caspase-9, release of cytochrome c from the mitochondria into the cytosol, and subsequent cleavage of poly (adenosine diphosphate-ribose polymerase (PARP. These findings show that the ZER-NLC is a potentially useful treatment for acute lymphoblastic leukemia in humans.Keywords: zerumbone-loaded nanostructured lipid carrier, cell cycle arrest, apoptosis, mitochondrial pathway

  7. Diploid clone produces unreduced diploid gametes but tetraploid clone generates reduced diploid gametes in the Misgurnus loach.

    Science.gov (United States)

    Morishima, Kagayaki; Yoshikawa, Hiroyuki; Arai, Katsutoshi

    2012-02-01

    Most individuals of the loach Misgurnus anguillicaudatus reproduce bisexually, but cryptic clonal lineages reproduce by natural gynogenesis of unreduced diploid eggs that are genetically identical to maternal somatic cells. Triploid progeny often occur by the accidental incorporation of a sperm nucleus into diploid eggs. Sex reversal from a genetic female to a physiological male is easily induced in this species by androgen treatment and through environmental influences. Here, we produced clonal tetraploid individuals by two methods: 1) fertilization of diploid eggs from a clonal diploid female with diploid sperm of a hormonally sex-reversed clonal diploid male and 2) artificial inhibition of the release of the second polar body in eggs of clonal diploid females just after initiation of gynogenetic development. There is no genetic difference between the clonal diploid and tetraploid individuals except for the number of chromosome sets or genomes. Clonal tetraploid males never produced unreduced tetraploid sperm, only diploid sperm that were genetically identical to those of a clonal diploid. Likewise, clonal tetraploid females did not form unreduced tetraploid eggs, just diploid eggs. However, the eggs' genotypes were identical to those of the original clone, and almost all the eggs initiated natural gynogenesis. Thus, gametogenesis of the clonal tetraploid loach is controlled by the presence of two chromosome sets to pair, thereby preserving the normal meiotic process, i.e., the formation of bivalents and subsequently two successive divisions.

  8. Study on stability of poliomyelitis vaccine in dragee candy (human diploid cell), live%口服脊髓灰质炎减毒活疫苗(人二倍体细胞)的稳定性研究

    Institute of Scientific and Technical Information of China (English)

    张晋; 王红燕; 张亮; 梁晶; 徐冉; 金歌; 柯伟华

    2014-01-01

    Objective To evaluate the stability of poliomyelitis vaccine in dragee candy (human diploid cell), live, which is produced consecutively by using cell factory units .Methods The vaccine was stored at -20℃for 24 months, the vac-cine titer ( CCID50 ) , appearance , residual antibiotics , sterility and identification of serotypes for virus seeds were tested . The evaluation of vaccine stability stored at 2-8℃for 12 months., the accelerated thermal stability assay at room tempera-ture for 7 weeks and at 37 ℃ for 7 days were performed , resprctively .Results The duration of vaccine is at least 24 months stored at -20 ℃, the shelf life of vaccine can extend to 12 months stored at 2-8 ℃, and freezing-thawing cycles have little effect on vaccine ’ s stability.Conclusion The quality of the vaccine is stable , the test results are complied with requirements of poliomyelitis vaccine in dragee candy (human diploid cell), live in 《Pharmacopeia of People’s Republic of China》( Volume Ⅲ) ( Edition:2010 ) and TiantanBio licensed standard for poliomyelitis vaccine in dragee candy ( hu-man diploid cell ) , live.%目的:评价细胞工厂工艺连续生产的口服脊髓灰质炎减毒活疫苗(人二倍体细胞)的稳定性。方法疫苗在-20℃放置24个月,检测病毒滴度、外观、抗生素残留量、无菌性,及对病毒血清型进行鉴别;2~8℃放置12个月检测疫苗稳定性;室温放置7周、37℃放置7 d检测加速热稳定性并冻融的稳定性。结果该疫苗-20℃可贮存24个月以上,2~8℃有效期可延长至12个月,且冻融不会影响疫苗的稳定性。结论疫苗质量稳定,各项检测结果均符合《中华人民共和国药典》三部(2010版)及企业《口服脊髓灰质炎减毒活疫苗(人二倍体细胞)注册标准》。

  9. The diploid genome sequence of an Asian individual

    DEFF Research Database (Denmark)

    Wang, Jun; Wang, Wei; Li, Ruiqiang

    2008-01-01

    Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we...

  10. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

    Directory of Open Access Journals (Sweden)

    Itaru Kato

    Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

  11. CD90 and CD110 correlate with cancer stem cell potentials in human T-acute lymphoblastic leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hiroto; Nishida, Hiroko; Iwata, Satoshi [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Dang, Nam H. [Department of Hematologic Malignancies, Nevada Cancer Institute, Las Vegas, NV (United States); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan)

    2009-05-29

    Although cancer stem cells (CSCs) have been recently identified in myeloid leukemia, published data on lymphoid malignancy have been sparse. T-acute lymphoblastic leukemia (T-ALL) is characterized by the abnormal proliferation of T-cell precursors and is generally aggressive. As CD34 is the only positive-selection marker for CSCs in T-ALL, we performed extensive analysis of CD markers in T-ALL cell lines. We found that some of the tested lines consisted of heterogeneous populations of cells with various levels of surface marker expression. In particular, a small subpopulation of CD90 (Thy-1) and CD110 (c-Mpl) were shown to correlate with stem cell properties both in vitro and in transplantation experiments. As these markers are expressed on hematopoietic stem cells, our results suggest that stem cell-like population are enriched in CD90+/CD110+ fraction and they are useful positive-selection markers for the isolation of CSCs in some cases of T-ALL.

  12. Cellular proteolytic modification of tumor-suppressor CYLD is critical for the initiation of human T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Arora, Mansi; Kaul, Deepak; Varma, Neelam; Marwaha, R K

    2015-01-01

    There exists a general recognition of the fact that post translational modification of CYLD protein through proteolytic cleavage by MALT-1 results in sustained cellular NF-kB activity which is conspicuously found to be associated with cancer in general and hematological malignancies in particular. The present study was directed to understand the contribution of MALT-1 and deubiquitinase CYLD to the initiation of T-cell acute lymphoblastic leukemia (T-ALL). Such a study revealed for the first time that the 35kDa CYLD cleaved factor generated by MALT-1 mediated proteolytic cleavage was conspicuously present in human T- ALL subjects of pediatric age group. Further, over-expression of this 35kDa CYLD factor within normal human peripheral blood mononuclear cells had the inherent capacity to program the genome of these cells resulting in T-cell lineage ALL. Based upon these results, we propose that MALT1 inhibitors may be of crucial importance in the treatment of T-ALL subjects of pediatric age group.

  13. Manufacture of diploid/tetraploid chimeric mice.

    OpenAIRE

    Lu, T Y; Markert, C L

    1980-01-01

    Tetraploid mouse embryos were produced by cytochalasin B treatment. These embryos usually die before completion of embryonic development and are abnormal morphologically and physiologically. The tetraploid embryos can be rescued to develop to maturity by aggregating them with normal diploid embryos to produce diploid/tetraploid chimeric mice. The diploid/tetraploid chimeric embryos are frequently abnormal: the larger the proportion of tetraploid cells, the greater the abnormality. By karyotyp...

  14. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Ruiping; He, Mingyuan; Dong, Chen; Xie, Yuexia; Ye, Shuang; Yuan, Dexiao [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2013-01-15

    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles.

  15. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article...

  16. Induction of genomic instability in TK6 human lymphoblasts exposed to 137Cs gamma radiation: comparison to the induction by exposure to accelerated 56Fe particles

    Science.gov (United States)

    Evans, Helen H.; Horng, Min-Fen; Ricanati, Marlene; Diaz-Insua, M.; Jordan, Robert; Schwartz, Jeffrey L.

    2003-01-01

    The induction of genomic instability in TK6 human lymphoblasts by exposure to (137)Cs gamma radiation was investigated by measuring the frequency and characteristics of unstable clones isolated approximately 36 generations after exposure. Clones surviving irradiation and control clones were analyzed for 17 characteristics including chromosomal aberrations, growth defects, alterations in response to a second irradiation, and mutant frequencies at the thymidine kinase and Na(+)/K(+) ATPase loci. Putative unstable clones were defined as those that exhibited a significant alteration in one or more characteristics compared to the controls. The frequency and characteristics of the unstable clones were compared in clones exposed to (137)Cs gamma rays or (56)Fe particles. The majority of the unstable clones isolated after exposure to either gamma rays or (56)Fe particles exhibited chromosomal instability. Alterations in growth characteristics, radiation response and mutant frequencies occurred much less often than cytogenetic alterations in these unstable clones. The frequency and complexity of the unstable clones were greater after exposure to (56)Fe particles than to gamma rays. Unstable clones that survived 36 generations after exposure to gamma rays exhibited increases in the incidence of dicentric chromosomes but not of chromatid breaks, whereas unstable clones that survived 36 generations after exposure to (56)Fe particles exhibited increases in both chromatid and chromosome aberrations.

  17. Andrographolide inhibits growth of human T-cell acute lymphoblastic leukemia Jurkat cells by downregulation of PI3K/AKT and upregulation of p38 MAPK pathways.

    Science.gov (United States)

    Yang, Tingfang; Yao, Shuluan; Zhang, Xianfeng; Guo, Yan

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) as a prevalent hematologic malignancy is one of the most common malignant tumors worldwide in children. Andrographolide (Andro), the major active component from Andrographis paniculata, has been shown to possess antitumor activities in several types of cancer cells. However, whether Andro would inhibit T-ALL cell growth remains unclear. In this study, we investigated the cytotoxic effect of Andro on human T-ALL Jurkat cells and explored the mechanisms of cell death. Cell apoptosis was assayed by flow cytometry, and the signaling transduction for Andro was analyzed by Western blotting. The results indicated 10 μg/mL Andro could significantly induce Jurkat cells' apoptosis, depending on the inhibition of PI3K/AKT pathway. Moreover, Andro-induced apoptosis is enhanced by AKT-selective inhibitor LY294002. ERK- or JNK-selective inhibitors PD98059 and SP600125 had no effect on Andro-induced apoptosis. In addition, p38 inhibitor SB203580 could reverse Andro-induced apoptosis in Jurkat cells. We also found that the protein expression of p-p53 and p-p38 were increased after Andro treatments. The result of an in vivo study also demonstrated Andro's dose-dependent inhibition in subcutaneous Jurkat xenografts. In conclusion, our findings explained a novel mechanism of drug action by Andro in Jurkat cells and suggested that Andro might be developed into a new candidate therapy for T-ALL patients in the coming days.

  18. Bortezomib interferes with adhesion of B cell precursor acute lymphoblastic leukemia cells through SPARC up-regulation in human bone marrow mesenchymal stromal/stem cells.

    Science.gov (United States)

    Iwasa, Masaki; Miura, Yasuo; Fujishiro, Aya; Fujii, Sumie; Sugino, Noriko; Yoshioka, Satoshi; Yokota, Asumi; Hishita, Terutoshi; Hirai, Hideyo; Andoh, Akira; Ichinohe, Tatsuo; Maekawa, Taira

    2017-05-01

    The poor prognosis of adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is attributed to leukemia cells that are protected by the bone marrow (BM) microenvironment. In the present study, we explored the pharmacological targeting of mesenchymal stromal/stem cells in BM (BM-MSCs) to eliminate chemoresistant BCP-ALL cells. Human BCP-ALL cells (NALM-6 cells) that adhered to human BM-MSCs (NALM-6/Ad) were highly resistant to multiple anti-cancer drugs, and exhibited pro-survival characteristics, such as an enhanced Akt/Bcl-2 pathway and increased populations in the G0 and G2/S/M cell cycle stages. Bortezomib, a proteasome inhibitor, interfered with adhesion between BM-MSCs and NALM-6 cells and up-regulated the matricellular protein SPARC (secreted protein acidic and rich in cysteine) in BM-MSCs, thereby reducing the NALM-6/Ad population. Inhibition of SPARC expression in BM-MSCs using a small interfering RNA enhanced adhesion of NALM-6 cells. Conversely, recombinant SPARC protein interfered with adhesion of NALM-6 cells. These results suggest that SPARC disrupts adhesion between BM-MSCs and NALM-6 cells. Co-treatment with bortezomib and doxorubicin prolonged the survival of BCP-ALL xenograft mice, with a significant reduction of leukemia cells in BM. Our findings demonstrate that bortezomib contributes to the elimination of BCP-ALL cells through disruption of their adhesion to BM-MSCs, and offer a novel therapeutic strategy for BCP-ALL through targeting of BM-MSCs.

  19. Lymphoblastic leukemia in pregnancy

    OpenAIRE

    Rojas Castrillo, Yaoska; Guevara González, José Guillermo

    2015-01-01

    Acute Leukemia occurs mainly in age groups of children under 5 years and in elderly patients, however; can also be seen in women of reproductive age. The prevalence of adult acute leukemia in young pregnant women is very rare, one case in 75,000 pregnancies and only 28% of them correspond to Lymphoblastic Leukemia occurs. The association between Acute Lymphocytic Leukemia and pregnancy poses a complex situation where you should not take or delay treatment, but the use of antineoplastic drug c...

  20. Andrographolide inhibits growth of human T-cell acute lymphoblastic leukemia Jurkat cells by downregulation of PI3K/AKT and upregulation of p38 MAPK pathways

    Directory of Open Access Journals (Sweden)

    Yang T

    2016-04-01

    Full Text Available Tingfang Yang,1 Shuluan Yao,2 Xianfeng Zhang,3 Yan Guo2 1Department of Pediatrics, Jining No 1 People’s Hospital, Shandong Province, People’s Republic of China; 2Department of Respiratory Medicine, Jining Medical University Affiliated Hospital, Shandong Province, People’s Republic of China; 3Department of Psychiatry, Jining Psychiatric Hospital, Shandong Province, People’s Republic of China Abstract: T-cell acute lymphoblastic leukemia (T-ALL as a prevalent hematologic malignancy is one of the most common malignant tumors worldwide in children. Andrographolide (Andro, the major active component from Andrographis paniculata, has been shown to possess antitumor activities in several types of cancer cells. However, whether Andro would inhibit T-ALL cell growth remains unclear. In this study, we investigated the cytotoxic effect of Andro on human T-ALL Jurkat cells and explored the mechanisms of cell death. Cell apoptosis was assayed by flow cytometry, and the signaling transduction for Andro was analyzed by Western blotting. The results indicated 10 µg/mL Andro could significantly induce Jurkat cells’ apoptosis, depending on the inhibition of PI3K/AKT pathway. Moreover, Andro-induced apoptosis is enhanced by AKT-selective inhibitor LY294002. ERK- or JNK-selective inhibitors PD98059 and SP600125 had no effect on Andro-induced apoptosis. In addition, p38 inhibitor SB203580 could reverse Andro-induced apoptosis in Jurkat cells. We also found that the protein expression of p-p53 and p-p38 were increased after Andro treatments. The result of an in vivo study also demonstrated Andro’s dose-dependent inhibition in subcutaneous Jurkat xenografts. In conclusion, our findings explained a novel mechanism of drug action by Andro in Jurkat cells and suggested that Andro might be developed into a new candidate therapy for T-ALL patients in the coming days. Keywords: andrographolide, PI3K, AKT, Burkitt lymphoma, Jurkat cell

  1. Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Faderl, Stefan; O’Brien, Susan; Pui, Ching-Hon; Stock, Wendy; Wetzler, Meir; Hoelzer, Dieter; Kantarjian, Hagop M.

    2016-01-01

    Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. Although ALL is a success story in pediatric oncology, results in adults lag behind those in children. An expansion of new drugs, more reliable immunologic and molecular techniques for the assessment of minimal residual disease, and efforts at more precise risk stratification are generating new aspects of adult ALL therapy. For this review, the authors summarized pertinent and recent literature on ALL biology and therapy, and they discuss current strategies and potential implications of novel approaches to the management of adult ALL. PMID:20101737

  2. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-10-24

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  3. Aqueous extract of Crataegus azarolus protects against DNA damage in human lymphoblast Cell K562 and enhances antioxidant activity.

    Science.gov (United States)

    Mustapha, Nadia; Bouhlel, Inès; Chaabane, Fadwa; Bzéouich, Imèn Mokdad; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2014-02-01

    The present study was carried out to characterize the cellular antioxidant effect of the aqueous extract of Crataegus azarolus and its antigenotoxic potential using human myelogenous cells, K562. The antioxidant capacity of this extract was evaluated by determining its cellular antioxidant activity (CAA) in K562 cells. Also, preceding antigenotoxicity assessment, its eventual genotoxicity property was investigated by evaluating its capacity to induce the DNA degradation of treated cell nuclei. As no genotoxicity was detected at different exposure times, its ability to protect cell DNA against H2O2 oxidative effect was investigated, using the "comet assay." It appears that 800 μg/mL of extract inhibited the genotoxicity induced by H2O2 with a rate of 41.30 %, after 4 h of incubation. In addition, this extract revealed a significant cellular antioxidant capacity against the reactive oxygen species in K562 cells.

  4. Human parvovirus B19 DNA is not detected in Guthrie cards from children who have developed acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Isa, Adiba; Priftakis, Peter; Broliden, Kristina

    2004-01-01

    related to human diseases, including erythema infectiosum and aplastic crisis, but it has not yet been considered to be involved in the development of ALL. Therefore, the aim of this study was to investigate, whether prenatal B19 infection could still be indirectly correlated with the development...... of childhood ALL. PROCEDURES: Fifty-four Guthrie cards, collected at 3-5 days of age, from Swedish children who subsequently developed ALL, as well as from 50 healthy controls, were investigated by nested PCR for the presence of B19 DNA. RESULTS: B19 DNA was not detected in any of the Guthrie cards from ALL...... patients or from healthy controls, although all tested samples had amplifiable cellular DNA as confirmed by an HLA DQ specific PCR. CONCLUSION: B19 DNA was not found in any of the Guthrie cards from children who later developed ALL or in the healthy controls. These findings suggest that it is less likely...

  5. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Laura B Ramsey

    Full Text Available Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002. Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia.

  6. TGF-{beta} signals the formation of a unique NF1/Smad4-dependent transcription repressor-complex in human diploid fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Luciakova, Katarina, E-mail: katarina.luciakova@savba.sk [Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Vlarska 7, 833 91 Bratislava (Slovakia); Kollarovic, Gabriel; Kretova, Miroslava; Sabova, Ludmila [Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Vlarska 7, 833 91 Bratislava (Slovakia); Nelson, B. Dean [Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, S-106 91 Stockholm (Sweden)

    2011-08-05

    Highlights: {yields} TGF-{beta} induces the formation of unique nuclear NF1/Smad4 complexes that repress expression of the ANT-2 gene. {yields} Repression is mediated through an NF1-dependent repressor element in the promoter. {yields} The formation of NF1/Smad4 complexes and the repression of ANT2 are prevented by inhibitors of p38 kinase and TGF-{beta} RI. {yields} NF1/Smad complexes implicate novel role for NF1 and Smad proteins in the regulation of growth. -- Abstract: We earlier reported the formation of a unique nuclear NF1/Smad complex in serum-restricted fibroblasts that acts as an NF1-dependent repressor of the human adenine nucleotide translocase-2 gene (ANT2) [K. Luciakova, G. Kollarovic, P. Barath, B.D. Nelson, Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex, Biochem. J. 412 (2008) 123-130]. In the present study, we show that TGF-{beta}, like serum-restriction: (a) induces the formation of NF1/Smad repressor complexes, (b) increases binding of the complexes to the repressor elements (Go elements) in the ANT2 promoter, and (c) inhibits ANT2 expression. Repression of ANT2 by TGF-{beta} is eliminated by mutating the NF1 binding sites in the Go repressor elements. All of the above responses to TGF-{beta} are prevented by inhibitors of TGF-{beta} RI and MAPK p38. These inhibitors also prevent NF1/Smad4 repressor complex formation and repression of ANT2 expression in serum-restricted cells, suggesting that similar signaling pathways are initiated by TGF-{beta} and serum-restriction. The present finding that NF1/Smad4 repressor complexes are formed through TGF-{beta} signaling pathways suggests a new, but much broader, role for these complexes in the initiation or maintenance of the growth-inhibited state.

  7. Functional rare males in diploid parthenogenetic Artemia.

    Science.gov (United States)

    Maccari, M; Gómez, A; Hontoria, F; Amat, F

    2013-09-01

    Functional males that are produced occasionally in some asexual taxa - called 'rare males' - raise considerable evolutionary interest, as they might be involved in the origin of new parthenogenetic lineages. Diploid parthenogenetic Artemia produce rare males, which may retain the ability to mate with females of related sexual lineages. Here, we (i) describe the frequency of male progeny in populations of diploid parthenogenetic Artemia, (ii) characterize rare males morphologically, (iii) assess their reproductive role, using cross-mating experiments with sexual females of related species from Central Asia and characterize the F1 hybrid offspring viability and (iv) confirm genetically both the identity and functionality of rare males using DNA barcoding and microsatellite loci. Our result suggests that these males may have an evolutionary role through genetic exchange with related sexual species and that diploid parthenogenetic Artemia is a good model system to investigate the evolutionary transitions between sexual species and parthenogenetic strains.

  8. Reinventing potato at the diploid level

    Science.gov (United States)

    We are positioned to revolutionize potato by reconstructing it as a diploid inbred-line based crop. Currently, potato is an asexually propagated cross-pollinated tetraploid crop, for which breeding methodologies have not changed substantially in 100 years. Current methods for creating new potato cul...

  9. Diploid/triploid mosaicism in dysmorphic patients

    NARCIS (Netherlands)

    van de Laar, [No Value; Rabelink, G; Hochstenbach, R; Tuerlings, J; Giltay, J

    2002-01-01

    Diploid/triploid mosaicism is a dysmorphology syndrome consisting of mental retardation, truncal obesity, body and/or facial asymmetry, growth retardation, hypotonia, a small phallus, malformed low-set ears and micrognathia. In 75% of the cases, the blood karyotype is normal and the diagnosis can on

  10. On the Genealogy of Asexual Diploids

    Science.gov (United States)

    Lam, Fumei; Langley, Charles H.; Song, Yun S.

    Given molecular genetic data from diploid individuals that, at present, reproduce mostly or exclusively asexually without recombination, an important problem in evolutionary biology is detecting evidence of past sexual reproduction (i.e., meiosis and mating) and recombination (both meiotic and mitotic). However, currently there is a lack of computational tools for carrying out such a study. In this paper, we formulate a new problem of reconstructing diploid genealogies under the assumption of no sexual reproduction or recombination, with the ultimate goal being to devise genealogy-based tools for testing deviation from these assumptions. We first consider the infinite-sites model of mutation and develop linear-time algorithms to test the existence of an asexual diploid genealogy compatible with the infinite-sites model of mutation, and to construct one if it exists. Then, we relax the infinite-sites assumption and develop an integer linear programming formulation to reconstruct asexual diploid genealogies with the minimum number of homoplasy (back or recurrent mutation) events. We apply our algorithms on simulated data sets with sizes of biological interest.

  11. Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-08-25

    B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  12. Speciation in arctic and alpine diploid plants

    OpenAIRE

    Gustafsson, A Lovisa S

    2013-01-01

    The main objectives of this thesis are to study patterns and processes of plant speciation in arctic and alpine diploid plants. Cryptic species are here referred to as morphologically similar individuals belonging to the same taxonomic species but that are unable to produce fertile offspring (i.e. 'sibling' species). The arctic flora is considered as one of the most species-poor floras of the world, and the latitudinal gradient with decreasing diversity from low to high latitudes is likely...

  13. Role of Ikaros in T-cell acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    Philippe; Kastner; Susan; Chan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.

  14. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  15. Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Jost, Tanja Rezzonico; Borga, Chiara; Radaelli, Enrico; Romagnani, Andrea; Perruzza, Lisa; Omodho, Lorna; Cazzaniga, Giovanni; Biondi, Andrea; Indraccolo, Stefano; Thelen, Marcus; Te Kronnie, Geertruy; Grassi, Fabio

    2016-06-01

    Infiltration of the central nervous system is a severe trait of T cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to the meninges without invasion of the brain parenchyma, in mice that underwent xenotransplantation with human T cell acute lymphoblastic leukemia cells or that developed leukemia from transformed hematopoietic progenitors. We tested the hypothesis that T cell acute lymphoblastic leukemia neuropathology results from meningeal infiltration through CXC chemokine receptor 4-mediated bone marrow colonization. Inhibition of leukemia engraftment in the bone marrow by pharmacologic CXC chemokine receptor 4 antagonism significantly ameliorated neuropathologic aspects of the disease. Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development. We hypothesize that lymphoblastic meningeal infiltration as a result of bone marrow colonization is responsible for the degenerative alterations of the neuroparenchyma as well as the alteration of cerebrospinal fluid drainage in T cell acute lymphoblastic leukemia xenografts. Therefore, CXC chemokine receptor 4 may constitute a pharmacologic target for T cell acute lymphoblastic

  16. Genome Size in Diploids, Allopolyploids, and Autopolyploids of Mediterranean Triticeae

    Directory of Open Access Journals (Sweden)

    T. Eilam

    2010-01-01

    Full Text Available Nuclear DNA amount, determined by the flow cytometry method, in diploids, natural and synthetic allopolyploids, and natural and synthetic autopolyploids of the tribe Triticeae (Poaceae is reviewed here and discussed. In contrast to the very small and nonsignificant variation in nuclear DNA amount that was found at the intraspecific level, the variation at the interspecific level is very large. Evidently changes in genome size are either the cause or the result of speciation. Typical autopolyploids had the expected additive DNA amount of their diploid parents, whereas natural and synthetic cytologically diploidized autopolyploids and natural and synthetic allopolyploids had significantly less DNA than the sum of their parents. Thus, genome downsizing, occurring during or immediately after the formation of these polyploids, provides the physical basis for their cytological diploidization, that is, diploid-like meiotic behavior. Possible mechanisms that are involved in genome downsizing and the biological significance of this phenomenon are discussed.

  17. Spatially explicit non-Mendelian diploid model

    CERN Document Server

    Lanchier, N; 10.1214/09-AAP598

    2009-01-01

    We introduce a spatially explicit model for the competition between type $a$ and type $b$ alleles. Each vertex of the $d$-dimensional integer lattice is occupied by a diploid individual, which is in one of three possible states or genotypes: $aa$, $ab$ or $bb$. We are interested in the long-term behavior of the gene frequencies when Mendel's law of segregation does not hold. This results in a voter type model depending on four parameters; each of these parameters measures the strength of competition between genes during meiosis. We prove that with or without a spatial structure, type $a$ and type $b$ alleles coexist at equilibrium when homozygotes are poor competitors. The inclusion of a spatial structure, however, reduces the parameter region where coexistence occurs.

  18. Oral Cancer Genesis and Progression: DNA Near-Diploid Aneuploidization and Endoreduplication by High Resolution Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Alessandra Donadini

    2010-01-01

    Full Text Available Oral potentially malignant lesions (OPMLs with dysplasia and aneuploidy are thought to have a high risk of progression into oral squamous cell carcinomas (OSCCs. Non-dysplastic “oral distant fields” (ODFs, characterized by clinically normal appearing mucosa sited at a distance from co-existing OPMLs, and non-dysplastic OPMLs may also represent an early pre-cancerous state. ODFs, OPMLs without and with dysplasia and OSCCs were investigated by high resolution DNA content flow cytometry (FCM. ODFs and OPMLs without dysplasia were DNA aneuploid respectively in 7/82 (8.5% and 25/109 (23% cases. “True normal oral mucosa” and human lymphocytes from healthy donors were DNA diploid in all cases and were used as sex specific DNA diploid controls. Dysplastic OPMLs and OSCCs were DNA aneuploid in 12/26 (46% and 12/13 (92% cases. The DNA aneuploid sublines were characterized by the DNA Index (DI ≠ 1. Aneuploid sublines in ODFs and in non-dysplastic and dysplastic OPMLs were near-diploid (DI < 1.4 respectively in all, 2/3 and 1/3 of the cases. DNA aneuploid OSCCs, instead, were characterized prevalently by multiple aneuploid sublines (67%, which were commonly (57% high-aneuploid (DI ≥ 1.4. DNA near-diploid aneuploid sublines in ODFs and OPMLs appear as early events of the oral carcinogenesis in agreement with the concept of field effect. Near-diploid aneuploidization is likely to reflect mechanisms of loss of symmetry in the chromosome mitotic division. High DNA aneuploid and multiple sublines in OPMLs with dysplasia and OSCCs suggest, instead, mechanisms of “endoreduplication” of diploid and near-diploid aneuploid cells and chromosomal loss. High resolution DNA FCM seems to enable the separation of subsequent progression steps of the oral carcinogenesis.

  19. Flow injection amperometric sandwich-type aptasensor for the determination of human leukemic lymphoblast cancer cells using MWCNTs-Pdnano/PTCA/aptamer as labeled aptamer for the signal amplification.

    Science.gov (United States)

    Amouzadeh Tabrizi, Mahmoud; Shamsipur, Mojtaba; Saber, Reza; Sarkar, Saeed

    2017-09-08

    In this research, we demonstrated a flow injection amperometric sandwich-type aptasensor for the determination of human leukemic lymphoblasts (CCRF-CEM) based on poly(3,4-ethylenedioxythiophene) decorated with gold nanoparticles (PEDOT-Aunano) as a nano platform to immobilize thiolated sgc8c aptamer and multiwall carbon nanotubes decorated with palladium nanoparticles/3,4,9,10-perylene tetracarboxylic acid (MWCNTs-Pdnano/PTCA) to fabricate catalytic labeled aptamer. In the proposed sensing strategy, the CCRF-CEM cancer cells were sandwiched between immobilized sgc8c aptamer on PEDOT-Aunano modified surface electrode and catalytic labeled sgc8c aptamer (MWCNTs-Pdnano/PTCA/aptamer). After that, the concentration of CCRF-CEM cancer cells was determined in presence of 0.1 mM hydrogen peroxide (H2O2) as an electroactive component. The attached MWCNTs-Pdnano nanocomposites to CCRF-CEM cancer cells amplified the electrocatalytic reduction of H2O2 and improved the sensitivity of the sensor to CCRF-CEM cancer cells. The MWCNT-Pdnano nanocomposite was characterized with transmission electron microscopy (TEM) and energy dispersive X-ray (EDX). The electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to confirm the stepwise changes in the electrochemical surface properties of the electrode. The proposed sandwich-type electrochemical aptasensor exhibited an excellent analytical performance for the detection of CCRF-CEM cancer cells ranging from 1.0 × 10(1) to 5.0 × 10(5) cells mL(-1). The limit of detection was 8 cells mL(-1). The proposed aptasensor showed high selectivity toward CCRF-CEM cancer cells. The proposed aptasensor was also applied to the determination of CCRF-CEM cancer cells in human serum samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. SSR Analysis of Genetic Diversity Among 192 Diploid Potato Cultivars

    Directory of Open Access Journals (Sweden)

    Xiaoyan Song

    2016-05-01

    Full Text Available In potato breeding, it is difficult to improve the traits of interest at the tetraploid level due to the tetrasomic inheritance. A promising alternative is diploid breeding. Thus it is necessary to assess the genetic diversity of diploid potato germplasm for efficient exploration and deployment of desirable traits. In this study, we used SSR markers to evaluate the genetic diversity of diploid potato cultivars. To screen polymorphic SSR markers, 55 pairs of SSR primers were employed to amplify 39 cultivars with relatively distant genetic relationships. Among them, 12 SSR markers with high polymorphism located at 12 chromosomes were chosen to evaluate the genetic diversity of 192 diploid potato cultivars. The primers produced 6 to 18 bands with an average of 8.2 bands per primer. In total, 98 bands were amplified from 192 cultivars, and 97 of them were polymorphic. Cluster analysis using UPGMA showed the genetic relationships of all accessions tested: 186 of the 192 accessions could be distinguished by only 12 pairs of SSR primers, and the 192 diploid cultivars were divided into 11 groups, and 83.3% constituted the first group. Clustering results showed relatively low genetic diversity among 192 diploid cultivars, with closer relationship at the molecular level. The results can provide molecular basis for diploid potato breeding.

  1. A diploid wheat TILLING resource for wheat functional genomics

    Directory of Open Access Journals (Sweden)

    Rawat Nidhi

    2012-11-01

    Full Text Available Abstract Background Triticum monococcum L., an A genome diploid einkorn wheat, was the first domesticated crop. As a diploid, it is attractive genetic model for the study of gene structure and function of wheat-specific traits. Diploid wheat is currently not amenable to reverse genetics approaches such as insertion mutagenesis and post-transcriptional gene silencing strategies. However, TILLING offers a powerful functional genetics approach for wheat gene analysis. Results We developed a TILLING population of 1,532 M2 families using EMS as a mutagen. A total of 67 mutants were obtained for the four genes studied. Waxy gene mutation frequencies are known to be 1/17.6 - 34.4 kb DNA in polyploid wheat TILLING populations. The T. monococcum diploid wheat TILLING population had a mutation frequency of 1/90 kb for the same gene. Lignin biosynthesis pathway genes- COMT1, HCT2, and 4CL1 had mutation frequencies of 1/86 kb, 1/92 kb and 1/100 kb, respectively. The overall mutation frequency of the diploid wheat TILLING population was 1/92 kb. Conclusion The mutation frequency of a diploid wheat TILLING population was found to be higher than that reported for other diploid grasses. The rate, however, is lower than tetraploid and hexaploid wheat TILLING populations because of the higher tolerance of polyploids to mutations. Unlike polyploid wheat, most mutants in diploid wheat have a phenotype amenable to forward and reverse genetic analysis and establish diploid wheat as an attractive model to study gene function in wheat. We estimate that a TILLING population of 5, 520 will be needed to get a non-sense mutation for every wheat gene of interest with 95% probability.

  2. Comparative Genetics of Floral Morphology in Diploid and Allotetraploid Gossypium

    Institute of Scientific and Technical Information of China (English)

    CHEE Peng W

    2008-01-01

    @@ The cultivated Gossypium A genome diploid species G.arboreum and G.herbaceum and the allotetraploid species G.hirsutum and G.barbadense share common morphology for various floral traits,which offers an ideal system in which to investigate genetic mechanisms that differentiate diploid and tetraploid genomes.For example,knowing how a single phenotype behaves in the diploids,and comparing the same trait with different dosage effects in the tetraploids,may provide a means to study inter- and intra-genomic interactions in the polyploid genome.

  3. Antiproliferative potential of a novel parthenin analog P16 as evident by apoptosis accompanied by down-regulation of PI3K/AKT and ERK pathways in human acute lymphoblastic leukemia MOLT-4 cells.

    Science.gov (United States)

    Goswami, Akshra; Shah, Bhahwal Ali; Kumar, Ajay; Rizvi, Masood Ahmad; Kumar, Suresh; Bhushan, Shashi; Malik, Fayaz Ahmed; Batra, Navneet; Joshi, Amit; Singh, Jagtar

    2014-10-05

    Leukemia is one of the deadliest types of cancer. Lack of effective treatment strategies has resulted in an extensive quest for new therapeutic molecules against it. This study explores the molecular mechanism of anticancer activity of P16, a semisynthetic analog of parthenin, against the human acute lymphoblastic leukemia MOLT-4 cells. P16 displayed antiproliferative activity in different cancer cell lines; however, MOLT-4 cells showed highest sensitivity for P16 with IC50 value of 0.6μM. Further studies revealed that P16 induced cell death by apoptosis. It caused mitochondrial stress, which was mediated by the translocation of Bax from cytosol to mitochondria and release of cytochrome c into the cytosol and consequent activation of caspase-9. However, P16 was also able to activate caspase-8, thus involving both extrinsic and intrinsic pathways of apoptosis. Further, activation of caspase-3 led to cleavage of its target proteins PARP-1 and ICAD, which resulted in apoptotic DNA damage. P16 induced apoptosis was accompanied by the down-regulation of important leukemic cell survival proteins like pAKT (S473), pAKT (T308), pP70S6K, pCRAF, and pERK1/2. However, inhibition of caspases by Z-VAD-FMK reversed the down-regulatory effect of P16 on pAKT (S473) and pP70S6K, as evident by the cell viability assay and flow cytometric analysis but this inhibition did not completely reverse the antiproliferative effect of P16, thereby indicating the role of additional factors apart from caspases in P16 induced apoptosis in MOLT-4 cells. Owing to its antiproliferative potential against leukemia cells, P16 can further be explored as an effective therapeutics against leukemia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic ...

    African Journals Online (AJOL)

    Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic Arthritis in a Nigerian boy. ... lead to delay in commencing appropriate treatment. ... of two months duration, had an elevated Rheumatoid factor and X-ray findings suggestive of ...

  5. Acute lymphoblastic leukemia presenting with gross hematuria

    OpenAIRE

    Kalbani, Naifain Al; Weitzman, Sheila; Abdelhaleem, Mohamed; Carcao, Manuel; Abla, Oussama

    2007-01-01

    A case of a six-year-old boy presenting with gross hematuria is reported. Investigations revealed the etiology of the hematuria to be thrombocytopenia in the setting of newly diagnosed acute lymphoblastic leukemia. The diagnosis of leukemia was confirmed by bone marrow examination. The patient’s hematuria completely resolved with platelet transfusions. Although thrombocytopenia is a very common presenting feature of acute lymphoblastic leukemia, gross hematuria is exceedingly rare. Thus, thro...

  6. The Mediterranean: the cradle of Anthoxanthum (Poaceae) diploid diversity.

    Science.gov (United States)

    Chumová, Zuzana; Záveská, Eliška; Mandáková, Terezie; Krak, Karol; Trávnícek, Pavel

    2017-08-01

    Knowledge of diploid phylogeny and ecogeography provide a foundation for understanding plant evolutionary history, diversification patterns and taxonomy. The genus Anthoxanthum (vernal grasses, Poaceae) represents a taxonomically intricate polyploid complex with large phenotypic variation and poorly resolved evolutionary relationships. The aims of the study were to reveal: (1) evolutionary lineages of the diploid taxa and their genetic differentiation; (2) the past distribution of the rediscovered 'Mediterranean diploid'; and (3) possible migration routes of diploids in the Mediterranean. A combined approach involving sequencing of two plastid regions ( trnL-trnF and rpl32-trnL ), nrDNA ITS, rDNA FISH analyses, climatic niche characterization and spatio-temporal modelling was used. Among the examined diploid species, only two well-differentiated evolutionary lineages were recognized: Anthoxanthum gracile and A. alpinum . The other taxa - A. aristatum, A. ovatum, A. maderense and the 'Mediterranean diploid' - form a rather intermixed group based on the examined molecular data. In situ rDNA localization enabled identification of the ancestral Anthoxanthum karyotype, shared by A. gracile and two taxa from the crown group. For the studied taxa, ancestral location probabilities for six discrete geographical regions in the Mediterranean were proposed and likely scenarios of gradual expansion from them were suggested. Modelling past and present distributions shows that the 'Mediterranean diploid' has already been occurring in the same localities for 120 000 years. Highly congruent results were obtained and dated the origin and first diversification of Anthoxanthum to the Miocene. The later divergence probably took place in the Pleistocene and started polyploid evolution within the genus. The most recent diversification event is still occurring, and incomplete lineage sorting prevents full diversification of taxa at the molecular level, despite clear separation based on

  7. The canonical equation of adaptive dynamics for Mendelian diploids and haplo-diploids

    Science.gov (United States)

    Metz, Johan A. J.; de Kovel, Carolien G. F.

    2013-01-01

    One of the powerful tools of adaptive dynamics is its so-called canonical equation (CE), a differential equation describing how the prevailing trait vector changes over evolutionary time. The derivation of the CE is based on two simplifying assumptions, separation of population dynamical and mutational time scales and small mutational steps. (It may appear that these two conditions rarely go together. However, for small step sizes the time-scale separation need not be very strict.) The CE was derived in 1996, with mathematical rigour being added in 2003. Both papers consider only well-mixed clonal populations with the simplest possible life histories. In 2008, the CE's reach was heuristically extended to locally well-mixed populations with general life histories. We, again heuristically, extend it further to Mendelian diploids and haplo-diploids. Away from strict time-scale separation the CE does an even better approximation job in the Mendelian than in the clonal case owing to gene substitutions occurring effectively in parallel, which obviates slowing down by clonal interference. PMID:24516713

  8. Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Bommer, M.; Hütter, M.L.; Stilgenbauer, S.; de Hoog, G.S.; de Beer, Z.W.; Wellinghausen, N.

    2009-01-01

    We report to our knowledge the first case of human infection with Ophiostoma piceae. This Sporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for iden

  9. Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Bommer, M.; Hutter, M.L.; Stilgenbauer, S.; de Hoog, G.S.; de Beer, Z.W.; Wellinghausen, N.

    2009-01-01

    We report to our knowledge the first case of human infection with Ophiostoma piceae. This Sporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for iden

  10. In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties

    NARCIS (Netherlands)

    le Viseur, Christoph; Hotfilder, Marc; Bomken, Simon; Wilson, Kerrie; Roettgers, Silja; Schrauder, Andre; Rosemann, Annegret; Irving, Julie; Stam, Ronald W.; Shultz, Leonard D.; Harbott, Jochen; Juergens, Heribert; Schrappe, Martin; Pieters, Rob; Vormoor, Josef

    We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34

  11. Expression of α-amylase inhibitors in diploid Triticum species.

    Science.gov (United States)

    Zoccatelli, Gianni; Sega, Michela; Bolla, Michela; Cecconi, Daniela; Vaccino, Patrizia; Rizzi, Corrado; Chignola, Roberto; Brandolini, Andrea

    2012-12-15

    The aim of the work was to characterize the expression of various α-amylase inhibitors (αAIs), well known anti-nutritional compounds, for the development of healthier diploid wheat-based functional foods. The salt-soluble protein fractions from the seeds of 53 accessions among Triticum monococcum subsp. monococcum (T.m.), T. monococcum subsp. boeoticum (T.b.) and Triticum urartu (T.u.) were analyzed by immunoblotting after SDS-PAGE and Urea-PAGE using polyclonal antibodies (PABs) raised against 0.19 and 0.28 αAIs expressed in bread-wheat. Reverse zymography with human saliva and Tenebrio molitor α-amylases was used to assay inhibition activity. A great variability of the expression of αAI-related proteins was observed among T.b. and T.u. PABs, and reverse zymography revealed different bands, often not correlating with those present in bread-wheat. Two-dimensional electrophoresis followed by immunoblotting and mass spectrometric analysis identified these proteins as αAIs. Interestingly, no signal was observed within T.m. accessions. This makes T.m. an important candidate for the production of novel functional foods. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. A stable hybrid containing haploid genomes of two obligate diploid Candida species.

    Science.gov (United States)

    Chakraborty, Uttara; Mohamed, Aiyaz; Kakade, Pallavi; Mugasimangalam, Raja C; Sadhale, Parag P; Sanyal, Kaustuv

    2013-08-01

    Candida albicans and Candida dubliniensis are diploid, predominantly asexual human-pathogenic yeasts. In this study, we constructed tetraploid (4n) strains of C. albicans of the same or different lineages by spheroplast fusion. Induction of chromosome loss in the tetraploid C. albicans generated diploid or near-diploid progeny strains but did not produce any haploid progeny. We also constructed stable heterotetraploid somatic hybrid strains (2n + 2n) of C. albicans and C. dubliniensis by spheroplast fusion. Heterodiploid (n + n) progeny hybrids were obtained after inducing chromosome loss in a stable heterotetraploid hybrid. To identify a subset of hybrid heterodiploid progeny strains carrying at least one copy of all chromosomes of both species, unique centromere sequences of various chromosomes of each species were used as markers in PCR analysis. The reduction of chromosome content was confirmed by a comparative genome hybridization (CGH) assay. The hybrid strains were found to be stably propagated. Chromatin immunoprecipitation (ChIP) assays with antibodies against centromere-specific histones (C. albicans Cse4/C. dubliniensis Cse4) revealed that the centromere identity of chromosomes of each species is maintained in the hybrid genomes of the heterotetraploid and heterodiploid strains. Thus, our results suggest that the diploid genome content is not obligatory for the survival of either C. albicans or C. dubliniensis. In keeping with the recent discovery of the existence of haploid C. albicans strains, the heterodiploid strains of our study can be excellent tools for further species-specific genome elimination, yielding true haploid progeny of C. albicans or C. dubliniensis in future.

  13. Textural Analysis of Nuclear Mitotic Apparatus Antigen (NuMA Spatial Distribution in Interphase Nuclei from Human Drug-Resistant CEM Lymphoblasts

    Directory of Open Access Journals (Sweden)

    Naima Rafki‐Beljebbar

    1999-01-01

    Full Text Available In tumour cell lines, the resistance of cancer cells to a variety of structurally unrelated chemotherapeutic drugs is termed multidrug‐resistance or MDR. We reported previously that MDR leukemic cells displayed nuclear texture changes, as assessed by image cytometry. The nature of these changes remained uncertain but they could be associated with alterations of the nuclear matrix which could serve an important role in DNA organization and chromatin structure. Therefore, we have compared the textural features observed in G0/G1 nuclei from human leukemic CEM cells and their MDR variant CEM‐VLB, after staining of either DNA by Feulgen method or nuclear matrix by immunodetection of NuMA antigen on DNase treated samples. Chromatin or NuMA distributions within the nucleus were evaluated by image cytometry. Changes in textural parameters indicate that modifications of NuMA distribution observed in MDR cells are parallel to those observed at the whole chromatin level (i.e., a more decondensed and coarse texture with increase of Energy and Long‐run sections and decrease of Contrast and Short‐run sections. Moreover, Optical Densities measurements indicate that MDR cells seem to contain less NuMA, a datum confirmed by immunoblotting of nuclear proteins. In conclusion, chromatin changes observed by image cytometry in drug‐resistant human leukemic CEM cells appear associated with modifications of the nuclear matrix structure.

  14. Study on Safety and Immunogenicity of Oral Poliomyelitis Attenuated Live Vaccine (Human Diploid Cell)%口服脊髓灰质炎减毒活疫苗(人二倍体细胞)的安全性与免疫原性研究

    Institute of Scientific and Technical Information of China (English)

    郭绍红; 马福宝; 陈海平; 陶红; 英志芳; 张龙华; 高君; 李丽; 郜晓智; 王泽明; 杨云凯

    2010-01-01

    目的 评价口服脊髓灰质炎(脊灰)减毒活疫苗(人二倍体细胞)[Oral Poliomyelitis Attenuated Live Vaccine(Human Diploid Cell),OPV(HDC)],在≥2月龄儿童中的安全性和免疫原性.方法 采用随机、盲态、对照的原则进行设计,1200名2~5月龄婴儿随机接种OPV(HDC)和对照疫苗,用抗脊灰病毒中和抗体试验检测免疫前、后抗体.结果 接种3剂OPV(HDC)后全身反应轻微,全程免疫后1个月,Ⅰ、Ⅱ、Ⅲ型中和抗体免疫成功率分别为98.28%、95.32%、95.34%;免疫后易感人群的Ⅰ、Ⅱ、Ⅲ型中和抗体几何甲均滴度,分别为1:1243.72、1:234.38、1:273.10.结论 OPV(HDC)在≥2月龄儿童中具有良好的安全性和免疫原性.

  15. Fixation Probability in a Haploid-Diploid Population.

    Science.gov (United States)

    Bessho, Kazuhiro; Otto, Sarah P

    2017-01-01

    Classical population genetic theory generally assumes either a fully haploid or fully diploid life cycle. However, many organisms exhibit more complex life cycles, with both free-living haploid and diploid stages. Here we ask what the probability of fixation is for selected alleles in organisms with haploid-diploid life cycles. We develop a genetic model that considers the population dynamics using both the Moran model and Wright-Fisher model. Applying a branching process approximation, we obtain an accurate fixation probability assuming that the population is large and the net effect of the mutation is beneficial. We also find the diffusion approximation for the fixation probability, which is accurate even in small populations and for deleterious alleles, as long as selection is weak. These fixation probabilities from branching process and diffusion approximations are similar when selection is weak for beneficial mutations that are not fully recessive. In many cases, particularly when one phase predominates, the fixation probability differs substantially for haploid-diploid organisms compared to either fully haploid or diploid species. Copyright © 2017 by the Genetics Society of America.

  16. Comparative cytogenetic analysis of diploid and hexaploid Chenopodium album Agg

    Directory of Open Access Journals (Sweden)

    Bożena Kolano

    2011-01-01

    Full Text Available Two cytotypes of Chenopodium album, diploid (2n=2x=18 and hexaploid (2n=6x=54, were analysed using flow cytometry and a FISH experiment. The genome size was indicated as 1.795 pg for the diploid and 3.845 pg for the hexaploid plants which suggested genome downsizing in the evolution of hexaploid cytotype. Double FISH with 25S rDNA and 5S rDNA allowed three to five homologue chromosome pairs to be distinguished depending on the cytotype. The Variation in size and number of rDNA sites between the polyploid C. album and its putative diploid ancestor indicated that rDNA loci underwent rearrangements after polyploidization. Flow cytometry measurements of the relative nuclear DNA content in the somatic tissue of C. album revealed extensive endopolyploidization resulting in tissues comprising a mixture of cells with a different DNA content (from 2C to 32C in varying proportions. The pattern of endopolyploidy was characteristic for the developmental stage of the plant and for the individual organ. Polysomaty was not observed in the embryo tissues however endopolyploidization had taken place in most tested organs of seedlings. The endopolyploidy in diploid and hexaploid C. album was compared to find any relationship between the pattern of polysomaty and polyploidy level in this species. This revealed that polyploid plants showed a decline in the number of endocycles as well as in the frequency of endopolyploidy cells compared to diploid plants.

  17. Lymphoblastic lymphoma involving multiple vertebrae.

    Science.gov (United States)

    Li, Da; Xu, Yu-Lun; Wu, Zhen

    2017-09-26

    Acute lymphoblastic lymphoma (ALL) was a malignant hematological disease in childhood but rarely, initially involved epidural compartment in adult. A 20-year-old male presented with progressive osphyalgia for 2 months and left lower motor weakness for 2 weeks with constipation. Physical examination revealed decreased muscle strength and numbness of left lower limb, and abnormal gait. Contrasted MRI showed multiple vertebrae of hypointense T1 signals (C2/C4/C7/T5/T8/T9/T12/L2/L4) and an intraspinal epidural lesion (L2-4). Subtotal resection was achieved. Histopathology suggested malignant B-cell lymphoma with Ki-67 of 90% and positivity of leukocyte common antigen (LCA). A bone marrow biopsy was unequivocally diagnostic of B-cell ALL followed by chemotherapy (Methotrexate) and partial recovery was observed. The present case was the oldest patient with epidural ALL. The radiographic changes in multiple vertebrae suggested metabolic, hematological, or granulomatous disease. The marrow biopsy was necessary if without hypercalcemia and abnormal peripheral blood examination. Accurate pathological diagnosis was essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Molecular diagnosis of lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Kalal Iravathy Goud

    2013-01-01

    Full Text Available The mixed lineage leukemia (MLL gene at chromosome band 11q23 is commonly involved in reciprocal translocations that is detected in acute leukemia. The MLL gene, coomonly known as mixed lineage leukemia or myeloid lymphoid leukemia, has been independently identified and cloned from the 11q23 breakpoint of acute leukemia. We describe a patient with acute lymphoblastic leukemia whose cells had shown reciprocal translocation between short arm (p21 of chromosome 2 and long arm (q23 of chromosome number 11 [t(2;11 (p21;q23] by cytogenetic analysis. Fluorescence in situ hybridization analysis (FISH was also performed for reconfirmation with a probe for MLL which showed split signals, hybridizing to both the derivative 2 and 11 chromosomes. Our study confirmed FISH as the most suitable assay for detecting MLL rearrangements because of its sensitivity and speed. It recommended that FISH should be used as complementary to conventional cytogenetic analysis. In conclusion, evaluation of the t(2;11(p21;q23 was done by molecular clarification and flow cytometry.

  19. Dissecting the Entry Route of Saporin-based a-CD7 Immunotoxins in Human T-Cell Acute Lymphoblastic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Maria Serena Fabbrini

    2013-01-01

    Full Text Available Elucidating the intracellular fate(s of targeted toxins is of fundamental importance for their optimal use as anticancer drugs, since the biochemical targets of their enzymatic activity reside in the cell cytoplasm, as in the case of the plant ribosome inactivating proteins (RIP saporin, ricin and of bacterial toxins. In this paper, we compared the cell surface binding and cytotoxic properties of the model RIP ricin to an immunotoxin constructed with a monoclonal antibody directed against the human T-cell marker CD7 covalently linked to saporin (CD7-SAP. Our results indicate that, despite the fact that internalization takes place via an apparently common entry route leading to the Golgi complex, surprisingly, the addition of an endoplasmic reticulum retrieval C-terminal signal (KDEL to CD7-SAP does not potentiate its cytotoxicity. In addition, while ricin toxicity is clearly reduced by Brefeldin A under conditions where this fungal metabolite causes Golgi stack disruption, we paradoxically observed a potentiating effect by Brefeldin A on CD7-SAP cytotoxicity suggesting that this inhibitor interferes with retrograde route(s other than the well established Trans-Golgi Network-ER retrograde route.

  20. Diploid male production in a leaf-cutting ant

    DEFF Research Database (Denmark)

    Armitage, S.; Boomsma, J.; Baer, Boris

    2010-01-01

    assumed to have reduced fitness compared with their haploid brothers. 2. While studying the reproductive biology of a leaf-cutting ant, Atta sexdens, in Gamboa, Republic of Panama, we detected the presence of a larger male morph. Using microsatellite markers we were able to confirm that the large male...... morph was diploid in 87% of cases. 3. We infer that the Gamboa population of A. sexdens experiences inbreeding depression because diploid males were found in three out of five mature colonies. However, their frequencies were relatively low because queens were multiply mated and our estimates suggest...... would be reduced compared with haploid males if they were able to copulate. 5. We conclude that diploid male production is likely to affect the fitness of A. sexdens queens with a matched mating, as these males are produced at the cost of workers and, if the colony survives to reach mature size, also...

  1. Comparison of Taste Components between Triploid and Diploid Oyster

    Institute of Scientific and Technical Information of China (English)

    LIN Hong; WANG Xiaoxue; ZHANG Bin; TANG Haiqing; XUE Changhu; XU Jiachao

    2002-01-01

    The main taste components of triploid and diploid oyster (Crassostrea gigas) were compared. Free amino acids,inosine monophosphate, succinate, trimethylamine oxide and betaine in fresh and boiled extractives were analyzed. The protein, lipids, glycogen, moisture and ash, which may affect the flavour, were evaluated. In boiled extractives, the amino acids were 394.1 mg(100 g)-1 in diploid and 183.5 mg(100 g)-1 in triploid. However, in fresh oyster extractives, they were 320.0 mg(100 g)-1 and 147.3 mg(100 g)-1 respectively. The inosine monophosphate in triploid was 44% more than that in diploid, and a little difference existed in the content of trimethylamine oxide between them. The contents of these taste components were the basis for taste flavour pattern determination.

  2. New type of postirradiation recovery of diploid yeast Saccharomyces cerevisae

    Energy Technology Data Exchange (ETDEWEB)

    Glazunov, A.V.; Kapul' tsevich, Yu.G. (Vsesoyuznyj Nauchno-Issledovatel' skij Inst. Genetiki i Selektsii Promyshlennykh Mikroorganizmov, Moscow (USSR))

    It was shown that the survival of diploid yeast Saccharomyces cerevisiae plated on the nutrient medium containing 8% NaCl rapidly increases with time of postirradiation keeping the cells in water at 28 deg C. The process is completed in 30-40 min. One fails to observe this phenomenon with the exposed cells plated on a standard culture medium for, in this case, the recovery has been fully completed before the first postirradiation division occurs. Haploid yeast Saccharomyces cerevisiae and diploid Pichia pinus are not capable of ''rapid'' repair of the studied type.

  3. Sequencing of a Cultivated Diploid CottonGenome-Gossypium arboreum

    Institute of Scientific and Technical Information of China (English)

    WILKINS Thea A

    2008-01-01

    @@ Sequencing the genomes of crop species and model systems contributes significantly to our under-standing of the organization,structure and function of plant genomes.In a "white paper" published in2007,the cotton community set forth a strategic plan for sequencing the AD genome of cultivated up-land cotton that initially targets less complex diploid genomes.This strategy banks on the high degreeof conservation between diploid progenitors and AD species that will allow information derived fromdiploid genomes to be directly applied to the tetraploids.

  4. Differential gene expression and alternative splicing between diploid and tetraploid watermelon lines

    Science.gov (United States)

    Synthetic tetraploid plants have been used for production of seedless triploid watermelon lines being pollinated with diploid plants. When compared to their diploid or triploid counterparts, the tetraploid exhibit wide phenotypic differences. Though many factors, including alternative splicing (AS),...

  5. Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic ...

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-04-28

    Apr 28, 2013 ... Acute lymphoblastic leukaemia (ALL) accounts for about 77% of cases ... tosis with a White Blood Cell count (WBC) of greater than 30 x 109/L and ... tarsometatarsal, small interphalangeal joints of the feet and vertebrae.3 Our ...

  6. Childhood acute lymphoblastic leukaemia and birthweight

    DEFF Research Database (Denmark)

    Roman, Eve; Lightfoot, Tracy; Smith, Alexandra G

    2013-01-01

    BACKGROUND: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes ( 4500 g), we pooled data from three of the largest childhood cancer case...

  7. Reproductive capacity of neo-tetraploid loaches produced using diploid spermatozoa from a natural tetraploid male

    OpenAIRE

    Fujimoto, Takafumi; Yasui, George Shigueki; Hayakawa, Mayumi; Sakao, Suzu; Yamaha, Etsuro; Arai, Katsutoshi

    2010-01-01

    Tetraploid loaches have been discovered amongst specimens recovered from fish markets in Japan. These tetraploids can be used as a source of diploid gametes to assist the further expansion of ploidy manipulation. Here, we produced a first generation neo-tetraploid strain by fertilizing eggs from a normal diploid female with diploid spermatozoa from a natural tetraploid male, followed five minutes later by heat shock (42°C, 2 min duration) to inhibit release of the second polar body. Diploid s...

  8. Fertile diploid drones in africanized honeybees, Apis mellifera adansonii.

    Science.gov (United States)

    Chaud-Netto, J

    1977-02-15

    59 diploid drones of Apis mellifera adansonii, 12-37 days old, were tested for the presence of semen after provoked ejaculation; 13 drones ejaculated semen enough to be used in an instrumental insemination, but only three on them (5%) furnished 1 mm3 of semen. The problems referring to the attainment of descendants from the 2n drones are briefly discussed.

  9. Sequencing of a Cultivated Diploid Cotton Genome-Gossypium arboreum

    Institute of Scientific and Technical Information of China (English)

    WILKINS; Thea; A

    2008-01-01

    Sequencing the genomes of crop species and model systems contributes significantly to our understanding of the organization,structure and function of plant genomes.In a `white paper' published in 2007,the cotton community set forth a strategic plan for sequencing the AD genome of cultivated upland cotton that initially targets less complex diploid genomes.This strategy banks on the high degree

  10. Application of Gibberellic Acid on Diploid and Tetraploid Cotton Hybridization

    Institute of Scientific and Technical Information of China (English)

    AJAFARI-MOFIDABADI; A; RANJBERAN; F; SOLTANLOO; H

    2008-01-01

    Gibberellic acid growth regulator was used to develop interspecific hybrids between tetraploid and diploid species to increase the genetic variability in cotton.In order to retain bolls and seed set in triploid hybrids,emasculated flowers of two Gossypium hirsutum commercial varieties(Sahel and Sephid)

  11. Origin and Genetic Diversity of Diploid Parthenogenetic Artemia in Eurasia

    Science.gov (United States)

    Maccari, Marta; Amat, Francisco; Gómez, Africa

    2013-01-01

    There is wide interest in understanding how genetic diversity is generated and maintained in parthenogenetic lineages, as it will help clarify the debate of the evolution and maintenance of sexual reproduction. There are three mechanisms that can be responsible for the generation of genetic diversity of parthenogenetic lineages: contagious parthenogenesis, repeated hybridization and microorganism infections (e.g. Wolbachia). Brine shrimps of the genus Artemia (Crustacea, Branchiopoda, Anostraca) are a good model system to investigate evolutionary transitions between reproductive systems as they include sexual species and lineages of obligate parthenogenetic populations of different ploidy level, which often co-occur. Diploid parthenogenetic lineages produce occasional fully functional rare males, interspecific hybridization is known to occur, but the mechanisms of origin of asexual lineages are not completely understood. Here we sequenced and analysed fragments of one mitochondrial and two nuclear genes from an extensive set of populations of diploid parthenogenetic Artemia and sexual species from Central and East Asia to investigate the evolutionary origin of diploid parthenogenetic Artemia, and geographic origin of the parental taxa. Our results indicate that there are at least two, possibly three independent and recent maternal origins of parthenogenetic lineages, related to A. urmiana and Artemia sp. from Kazakhstan, but that the nuclear genes are very closely related in all the sexual species and parthenogegetic lineages except for A. sinica, who presumable took no part on the origin of diploid parthenogenetic strains. Our data cannot rule out either hybridization between any of the very closely related Asiatic sexual species or rare events of contagious parthenogenesis via rare males as the contributing mechanisms to the generation of genetic diversity in diploid parthenogenetic Artemia lineages. PMID:24376692

  12. Origin and genetic diversity of diploid parthenogenetic Artemia in Eurasia.

    Science.gov (United States)

    Maccari, Marta; Amat, Francisco; Gómez, Africa

    2013-01-01

    There is wide interest in understanding how genetic diversity is generated and maintained in parthenogenetic lineages, as it will help clarify the debate of the evolution and maintenance of sexual reproduction. There are three mechanisms that can be responsible for the generation of genetic diversity of parthenogenetic lineages: contagious parthenogenesis, repeated hybridization and microorganism infections (e.g. Wolbachia). Brine shrimps of the genus Artemia (Crustacea, Branchiopoda, Anostraca) are a good model system to investigate evolutionary transitions between reproductive systems as they include sexual species and lineages of obligate parthenogenetic populations of different ploidy level, which often co-occur. Diploid parthenogenetic lineages produce occasional fully functional rare males, interspecific hybridization is known to occur, but the mechanisms of origin of asexual lineages are not completely understood. Here we sequenced and analysed fragments of one mitochondrial and two nuclear genes from an extensive set of populations of diploid parthenogenetic Artemia and sexual species from Central and East Asia to investigate the evolutionary origin of diploid parthenogenetic Artemia, and geographic origin of the parental taxa. Our results indicate that there are at least two, possibly three independent and recent maternal origins of parthenogenetic lineages, related to A. urmiana and Artemia sp. from Kazakhstan, but that the nuclear genes are very closely related in all the sexual species and parthenogegetic lineages except for A. sinica, who presumable took no part on the origin of diploid parthenogenetic strains. Our data cannot rule out either hybridization between any of the very closely related Asiatic sexual species or rare events of contagious parthenogenesis via rare males as the contributing mechanisms to the generation of genetic diversity in diploid parthenogenetic Artemia lineages.

  13. JAK Mutations in High-Risk Childhood Acute Lymphoblastic Leukemia

    National Research Council Canada - National Science Library

    Charles G. Mullighan; Jinghui Zhang; Richard C. Harvey; J. Racquel Collins-Underwood; Brenda A. Schulman; Letha A. Phillips; Sarah K. Tasian; Mignon L. Loh; Xiaoping Su; Wei Liu; Meenakshi Devidas; Susan R. Atlas; I-Ming Chen; Robert J. Clifford; Daniela S. Gerhard; William L. Carroll; Gregory H. Reaman; Malcolm Smith; James R. Downing; Stephen P. Hunger; Cheryl L. Willman; Janet D. Rowley

    2009-01-01

    Pediatric acute lymphoblastic leukemia (ALL) is a heterogeneous disease consisting of distinct clinical and biological subtypes that are characterized by specific chromosomal abnormalities or gene mutations...

  14. CDX2 gene expression in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Hanaa H. Arnaoaut

    2014-06-01

    Full Text Available CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

  15. 6-Thioguanine Induces Mitochondrial Dysfunction and Oxidative DNA Damage in Acute Lymphoblastic Leukemia Cells*

    OpenAIRE

    Zhang, Fan; Fu, Lijuan; Wang, Yinsheng

    2013-01-01

    Thiopurines are among the most successful chemotherapeutic agents used for treating various human diseases, including acute lymphoblastic leukemia and chronic inflammation. Although metabolic conversion and the subsequent incorporation of 6-thioguanine (SG) nucleotides into nucleic acids are considered important for allowing the thiopurine drugs to induce their cytotoxic effects, alternative mechanisms may also exist. We hypothesized that an unbiased analysis of SG-induced perturbation of the...

  16. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Lahortiga, Idoya; De Keersmaecker, Kim; Van Vlierberghe, Pieter; Graux, Carlos; Cauwelier, Barbara; Lambert, Frederic; Mentens, Nicole; Beverloo, H Berna; Pieters, Rob; Speleman, Frank; Odero, Maria D; Bauters, Marijke; Froyen, Guy; Marynen, Peter; Vandenberghe, Peter; Wlodarska, Iwona; Meijerink, Jules P P; Cools, Jan

    2007-05-01

    We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.

  17. Coexistence analysis of diploid and triploid hybrid water frogs

    Science.gov (United States)

    Apri, M.; Suandi, D.; Soewono, E.

    2014-02-01

    A dynamical model for genotype distributions of all hybrid populations of Pelophylax esculentus in the absence of differential survival is studied here. Assuming that under natural condition the parental genotypes LL and RR do not survive into adult stage, the dynamic is then reduced into three-dimensional dynamical system of classes LR, LLR, LRR genotypes. Coexistence of diploid (LR) and triploid (LLR and LRR) genotypes is analyzed here.

  18. Selection on meiosis genes in diploid and tetraploid Arabidopsis arenosa.

    Science.gov (United States)

    Wright, Kevin M; Arnold, Brian; Xue, Katherine; Šurinová, Maria; O'Connell, Jeremy; Bomblies, Kirsten

    2015-04-01

    Meiotic chromosome segregation is critical for fertility across eukaryotes, and core meiotic processes are well conserved even between kingdoms. Nevertheless, recent work in animals has shown that at least some meiosis genes are highly diverse or strongly differentiated among populations. What drives this remains largely unknown. We previously showed that autotetraploid Arabidopsis arenosa evolved stable meiosis, likely through reduced crossover rates, and that associated with this there is strong evidence for selection in a subset of meiosis genes known to affect axis formation, synapsis, and crossover frequency. Here, we use genome-wide data to study the molecular evolution of 70 meiosis genes in a much wider sample of A. arenosa. We sample the polyploid lineage, a diploid lineage from the Carpathian Mountains, and a more distantly related diploid lineage from the adjacent, but biogeographically distinct Pannonian Basin. We find that not only did selection act on meiosis genes in the polyploid lineage but also independently on a smaller subset of meiosis genes in Pannonian diploids. Functionally related genes are targeted by selection in these distinct contexts, and in two cases, independent sweeps occurred in the same loci. The tetraploid lineage has sustained selection on more genes, has more amino acid changes in each, and these more often affect conserved or potentially functional sites. We hypothesize that Pannonian diploid and tetraploid A. arenosa experienced selection on structural proteins that mediate sister chromatid cohesion, the formation of meiotic chromosome axes, and synapsis, likely for different underlying reasons. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. [Diploid/triploid mosaicism: a variable but characteristic phenotype].

    Science.gov (United States)

    Natera-De Benito, Daniel; Poo, Pilar; Gean, Esther; Vicente-Villa, Asunción; García-Cazorla, Angels; Fons-Estupiña, M Carmen

    2014-08-16

    Introduccion. El mosaicismo diploide/triploide es una alteracion cromosomica poco frecuente. La produce un fallo en la division poscigotica durante el desarrollo embrionario. Da lugar a la coexistencia de dos lineas celulares con diferente constitucion cromosomica (46,XX y 69,XXX) en un mismo individuo. Su fenotipo clinico es caracteristico. Las alteraciones pigmentarias con un patron de distribucion que sigue las lineas de Blaschko son el principal signo guia, asi como las alteraciones de otros tejidos derivados del ectodermo. Casos clinicos. Describimos las caracteristicas clinicas de tres pacientes afectos de mosaicismo diploide/triploide y realizamos una comparacion de su fenotipo clinico con el de los casos publicados previamente en la bibliografia. Las alteraciones observadas con mayor frecuencia fueron alteraciones cutaneas, discapacidad intelectual, obesidad troncular, talla baja, hemihipertrofia, y manos pequeñas y estrechas con clino y camptodactilia. Las caracteristicas fenotipicas de nuestros pacientes fueron similares a las de los casos comunicados previamente. Aunque no existe un fenotipo unico y especifico asociado al mosaicismo diploide/triploide, existen malformaciones caracteristicas que conforman un sindrome malformativo bien definido. El cariotipo realizado en linfocitos de sangre periferica en las tres pacientes fue normal, y se logro el diagnostico mediante cariotipo en fibroblastos cultivados tras biopsia de piel hipopigmentada. Conclusiones. La presencia de discapacidad intelectual asociada a obesidad troncular, talla baja, hemihipertrofia o clino y camptodactilia, ademas de las alteraciones cutaneas, debe hacer pensar en la posible existencia de un mosaicismo diploide/triploide. En la mayoria de los casos, es necesario el estudio del cariotipo en los fibroblastos para llegar al diagnostico.

  20. Genome size and genome evolution in diploid Triticeae species.

    Science.gov (United States)

    Eilam, T; Anikster, Y; Millet, E; Manisterski, J; Sagi-Assif, O; Feldman, M

    2007-11-01

    One of the intriguing issues concerning the dynamics of plant genomes is the occurrence of intraspecific variation in nuclear DNA amount. The aim of this work was to assess the ranges of intraspecific, interspecific, and intergeneric variation in nuclear DNA content of diploid species of the tribe Triticeae (Poaceae) and to examine the relation between life form or habitat and genome size. Altogether, 438 plants representing 272 lines that belong to 22 species were analyzed. Nuclear DNA content was estimated by flow cytometry. Very small intraspecific variation in DNA amount was found between lines of Triticeae diploid species collected from different habitats or between different morphs. In contrast to the constancy in nuclear DNA amount at the intraspecific level, there are significant differences in genome size between the various diploid species. Within the genus Aegilops, the 1C DNA amount ranged from 4.84 pg in A. caudata to 7.52 pg in A. sharonensis; among genera, the 1C DNA amount ranged from 4.18 pg in Heteranthelium piliferum to 9.45 pg in Secale montanum. No evidence was found for a smaller genome size in annual, self-pollinating species relative to perennial, cross-pollinating ones. Diploids that grow in the southern part of the group's distribution have larger genomes than those growing in other parts of the distribution. The contrast between the low variation at the intraspecific level and the high variation at the interspecific one suggests that changes in genome size originated in close temporal proximity to the speciation event, i.e., before, during, or immediately after it. The possible effects of sudden changes in genome size on speciation processes are discussed.

  1. Reference genes for normalizing transcription in diploid and tetraploid Arabidopsis.

    Science.gov (United States)

    Wang, Haibin; Wang, Jingjing; Jiang, Jiafu; Chen, Sumei; Guan, Zhiyong; Liao, Yuan; Chen, Fadi

    2014-10-27

    Published transcription data from a set of 19 diploid Arabidopsis thaliana and 5 tetraploid (3 allo- and 2 auto- tetraploid) Arabidopsis accessions were re-analysed to identify reliable reference genes for normalization purposes. Five conventional and 16 novel reference genes previously derived from microarray data covering a wide range of abundance in absolute expression levels in diploid A. thaliana Col-0 were employed. Transcript abundance was well conserved for all 21 potential reference genes in the diploid A. thaliana accessions, with geNorm and NormFinder analysis indicating that AT5G46630, AT1G13320, AT4G26410, AT5G60390 and AT5G08290 were the most stable. However, conservation was less good among the tetraploid accessions, with the transcription of seven of the 21 genes being undetectable in all allotetraploids. The most stable gene was AT5G46630, while AT1G13440 was the unstable one. Hence, the choice of reference gene(s) for A. thaliana is quite wide, but with respect to the analysis of transcriptomic data derived from the tetraploids, it is probably necessary to select more than one reference gene.

  2. Direct mating between diploid sake strains of Saccharomyces cerevisiae.

    Science.gov (United States)

    Hashimoto, Shinji; Aritomi, Kazuo; Minohara, Takafumi; Nishizawa, Yoshinori; Hoshida, Hisashi; Kashiwagi, Susumu; Akada, Rinji

    2006-02-01

    Various auxotrophic mutants of diploid heterothallic Japanese sake strains of Saccharomyces cerevisiae were utilized for selecting mating-competent diploid isolates. The auxotrophic mutants were exposed to ultraviolet (UV) irradiation and crossed with laboratory haploid tester strains carrying complementary auxotrophic markers. Zygotes were then selected on minimal medium. Sake strains exhibiting a MATa or MATalpha mating type were easily obtained at high frequency without prior sporulation, suggesting that the UV irradiation induced homozygosity at the MAT locus. Flow cytometric analysis of a hybrid showed a twofold higher DNA content than the sake diploid parent, consistent with tetraploidy. By crossing strains of opposite mating type in all possible combinations, a number of hybrids were constructed. Hybrids formed in crosses between traditional sake strains and between a natural nonhaploid isolate and traditional sake strains displayed equivalent fermentation ability without any apparent defects and produced comparable or improved sake. Isolation of mating-competent auxotrophic mutants directly from industrial yeast strains allows crossbreeding to construct polyploids suitable for industrial use without dependence on sporulation.

  3. Malignant transformation of diploid human fibroblasts by transfection of oncogenes

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, J.J.

    1992-01-01

    This document consist of brief reports prepared by postdoctoral students supported by the project, each describing his accomplishments under the grant. Topics include (1) Malignant Transformation of MSU-1. 1 Cells by Gamma Radiation, (2) Correlation between Levels of ras Expression and Presence of Transformed Phenotypes Including Tumorigenicity, Using a Modulatable Promoter, (3) Relation between Specific rad Oncogene Expression, (4) Correlation of Genetic Changes in Fibroblastic Tumors with Malignancies, (5)Transformation of MSU-1.1 Cells by sis Oncogene, (6) Malignant Transformation of MSU-1.0 Cells, (7) Correlation of Urokinase Plasminogen Activation (mu-PA) with Malignant Phenotype, (8)Two Dimensional Gel Electrophoresis Studies of the Proteins of the Major Cell Strains of the MSU-1 Family of Cells, and (9) Correlation between Proteinase Activity Levels and Malignancy.

  4. Parallel expression evolution of oxidative stress-related genes in fiber from wild and domesticated diploid and polyploid cotton (Gossypium

    Directory of Open Access Journals (Sweden)

    Mittler Ron

    2009-08-01

    Full Text Available Abstract Background Reactive oxygen species (ROS play a prominent role in signal transduction and cellular homeostasis in plants. However, imbalances between generation and elimination of ROS can give rise to oxidative stress in growing cells. Because ROS are important to cell growth, ROS modulation could be responsive to natural or human-mediated selection pressure in plants. To study the evolution of oxidative stress related genes in a single plant cell, we conducted comparative expression profiling analyses of the elongated seed trichomes ("fibers" of cotton (Gossypium, using a phylogenetic approach. Results We measured expression changes during diploid progenitor species divergence, allopolyploid formation and parallel domestication of diploid and allopolyploid species, using a microarray platform that interrogates 42,429 unigenes. The distribution of differentially expressed genes in progenitor diploid species revealed significant up-regulation of ROS scavenging and potential signaling processes in domesticated G. arboreum. Similarly, in two independently domesticated allopolyploid species (G. barbadense and G. hirsutum antioxidant genes were substantially up-regulated in comparison to antecedent wild forms. In contrast, analyses of three wild allopolyploid species indicate that genomic merger and ancient allopolyploid formation had no significant influences on regulation of ROS related genes. Remarkably, many of the ROS-related processes diagnosed as possible targets of selection were shared among diploid and allopolyploid cultigens, but involved different sets of antioxidant genes. Conclusion Our data suggests that parallel human selection for enhanced fiber growth in several geographically widely dispersed species of domesticated cotton resulted in similar and overlapping metabolic transformations of the manner in which cellular redox levels have become modulated.

  5. Mixoploidía Diploide - Tetraploide: Primer Reporte en Nuestro Medio

    Directory of Open Access Journals (Sweden)

    Héctor Pimentel Benítez

    1999-09-01

    Full Text Available Se presenta un caso de mixoploidía diploide-tetraploide, con ligeros signos clínicos pertenecientes a esta condición de la poliploidía en humanos. Estudios citogenéticos a partir de cultivos de sangre periférica y fibroblastos de piel permitieron establecer la fórmula cromosómica 46,XX/92XXXX en la paciente. Se realiza correlación fenotipocariotipo, así como su presentación clínica. Este estudio de casos ayuda a enriquecer el conocimiento sobre esta condición, contribuye a su mejor diagnóstico y a dilucidar la etiología de síndromes malformativos inespecíficos.A case of diploid-tetraploid mixoploidy with mild clinical signs correspondoing to this condition of polyploidy in humans is presented. Cytogenetic studies based on cultures of peripheral blood and fibroblasts of skin allowed to obtain the 46,XX/92XXXX chromosomic formula in the patient. The phenotype-kariotype correlation was stablished and its clinical presentation was made. This study of cases helps to improve the knowledge about this condition, and it also contributes to have a better diagnosis and to dilucidate the etiology of unspecific syndromes of malformation.

  6. Characters that differ between diploid and haploid honey bee (Apis mellifera) drones.

    Science.gov (United States)

    Herrmann, Matthias; Trenzcek, Tina; Fahrenhorst, Hartmut; Engels, Wolf

    2005-12-30

    Diploid males have long been considered a curiosity contradictory to the haplo-diploid mode of sex determination in the Hymenoptera. In Apis mellifera, 'false' diploid male larvae are eliminated by worker cannibalism immediately after hatching. A 'cannibalism substance' produced by diploid drone larvae to induce worker-assisted suicide has been hypothesized, but it has never been detected. Diploid drones are only removed some hours after hatching. Older larvae are evidently not regarded as 'false males' and instead are regularly nursed by the brood-attending worker bees. As the pheromonal cues presumably are located on the surface of newly hatched bee larvae, we extracted the cuticular secretions and analyzed their chemical composition by gas chromatograph-mass spectrometry (GC-MS) analyses. Larvae were sexed and then reared in vitro for up to three days. The GC-MS pattern that was obtained, with alkanes as the major compounds, was compared between diploid and haploid drone larvae. We also examined some physical parameters of adult drones. There was no difference between diploid and haploid males in their weight at the day of emergence. The diploid adult drones had fewer wing hooks and smaller testes. The sperm DNA content was 0.30 and 0.15 pg per nucleus, giving an exact 2:1 ratio for the gametocytes of diploid and haploid drones, respectively. Vitellogenin was found in the hemolymph of both types of imaginal drones at 5 to 6 days, with a significantly lower titer in the diploids.

  7. Phenotypic traits variation among native diploid, native tetraploid and invasive tetraploid Senecio inaequidens DC. (Asteraceae

    Directory of Open Access Journals (Sweden)

    Monty, A.

    2010-01-01

    Full Text Available Senecio inaequidens DC. is a rapidly spreading plant invader in Europe. In its native range, it occurs at two co-existing diploid and tetraploid cytotypes. To date, only tetraploids are reported in Europe, even though invasive diploids were recorded in other parts of the world. We compared native diploid and both native and invasive tetraploid populations in common gardens in Europe for a suite of life history traits. Diploids were able to develop, showed high biomass production and produced more flower heads than tetraploids. In contrast, winter survival was null for diploids. It was low for native tetraploids, but reached 40% in invasive tetraploids. Results suggested that diploid cytotype tends to an annual life form when grown in Western Europe, with earlier and more abundant flowering. In contrast, the tetraploid cytotype was mainly perennial which may enhance its invasiveness.

  8. [Comparative study of the protein makeup in diploid and haploid forms of Saccharomyces and Pichia].

    Science.gov (United States)

    Temina, A V; Tolstorukov, I I; Korogodin, V I; Gololobov, A D

    1979-01-01

    The rates of growth, biomass accumulation, and electrophoretic spectra of mobile cytoplasmic proteins were studied with nonisogenous haploid and diploid cultures of Saccharomyces cerevisiae and Pichia guilliermondii as well as with isogenous haploid-diploid pairs of Saccharomyces cerevisiae and Pichia pinus. On a mineral medium with glucose, differences in these parameters in various yeast strains were found to be due to the genotype of a strain rather than to ploidy: nonisogenous haploid and diploid cultures displayed considerable and random variability of these properties while no differences were found in isogenous haploid-diploid pairs. Studies on solubility of protein fractions in various solvents made it possible to reveal differences connected with ploidy, namely: both in nonisogenous and isogenous haploid-diploid systems, the content of the water-soluble fraction decreased in diploid cultures.

  9. Tetraploid citrus rootstocks are more tolerant to salt stress than diploid.

    Science.gov (United States)

    Saleh, Basel; Allario, Thierry; Dambier, Dominique; Ollitrault, Patrick; Morillon, Raphaël

    2008-09-01

    Citrus trees are subject to several abiotic constraints such as salinity. Providing new rootstocks more tolerant is thus a requirement. In this article, we investigated salt stress tolerance of three tetraploid rootstock genotypes when compared to their respective diploid rootstocks (Poncirus trifoliata, Carrizo citrange, Cleopatra mandarin). Plant growth, leaf fall and ion contents were investigated. At the end of the experiment, leaf fall was observed only for diploid Poncirus trifoliata plants as well as chlorosis symptoms for Poncirus trifoliata and Carrizo citrange diploid plants. The diploid Cleopatra mandarin plants growth rate was not affected by salt stress and has even been increased for tetraploid Cleopatra mandarin. Ion contents investigation has shown lower accumulations of chloride ions in leaves of the tetraploid plants when compared to diploid plants. Our results suggest that citrus tetraploid rootstocks are more tolerant to salt stress than their corresponding diploid.

  10. The association between polyploidy and clonal reproduction in diploid and tetraploid Chamerion angustifolium.

    Science.gov (United States)

    Baldwin, Sarah J; Husband, Brian C

    2013-04-01

    Clonal reproduction is associated with the incidence of polyploidy in flowering plants. This pattern may arise through selection for increased clonality in polyploids compared to diploids to reduce mixed-ploidy mating. Here, we test whether clonal reproduction is greater in tetraploid than diploid populations of the mixed-ploidy plant, Chamerion angustifolium, through an analysis of the size and spatial distribution of clones in natural populations using AFLP genotyping and a comparison of root bud production in a greenhouse study. Natural tetraploid populations (N = 5) had significantly more AFLP genotypes (x¯ = 10.8) than diploid populations (x¯ = 6.0). Tetraploid populations tended to have fewer ramets per genotype and fewer genotypes with >1 ramet. In a spatial autocorrelation analysis, ramets within genotypes were more spatially aggregated in diploid populations than in tetraploid populations. In the greenhouse, tetraploids allocated 90.4% more dry mass to root buds than diploids, but tetraploids produced no more root buds and 44% fewer root buds per unit root mass than diploids. Our results indicate that clonal reproduction is significant in most populations, but tetraploid populations are not more clonal than diploids, nor are their clones more spatially aggregated. As a result, tetraploids may be less sheltered from mixed-ploidy mating and diploids more exposed to inbreeding, the balance of which could influence the establishment of tetraploids in diploid populations.

  11. Mediastinal involvement in adults with lymphoblastic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, E.E.; Conroy, J.F.; Bonner, H.

    Radiologic, clinical, and pathologic findings are described in 6 young adults with lymphoblastic lymphoma (LBL), an aggressive tumor which has recently become recognized as a serious threat to adults as well as to children. Each patient presented with a mediastinal mass, three of them developing cardiac tamponade and one a superior vena cava syndrome. CT scanning and echocardiography were particularly helpful in defining the lesions. The rapid dissemination of LBL, and its early progression to a leukemic phase call for promt diagnosis and treatment.

  12. Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michael James Burke

    2014-05-01

    Full Text Available Aberrant epigenetic modifications are well-recognized drivers for oncogenesis. Pediatric acute lymphoblastic leukemia (ALL is no exception and serves as a model toward the significant impact these heritable alterations can have in leukemogenesis. In this brief review, we will focus on the main aspects of epigenetics which control leukemogenesis in pediatric ALL, mainly DNA methylation, histone modification and microRNA alterations. As we continue to gain better understanding of the driving mechanisms for pediatric ALL at both diagnosis and relapse, therapeutic interventions directed toward these pathways and mechanisms can be harnessed and introduced into clinical trials for pediatric ALL.

  13. Development of Permanent Mapping Populations RILs in Diploid A Genome

    Institute of Scientific and Technical Information of China (English)

    WAGHMARE VIJAY N; DONGRE A B; GOTMARE Vinita; PATIL P G; DESHPANDE L A; KHADI B M

    2008-01-01

    @@ Recombinant inbred lines (RILs) serve as powerful tools for genetic mapping.RILs are obtained by crossing two inbred lines followed by repeated selfing or sib-mating to create a set of new inbred lines.The resulting genome in the finally developed RILs is a mosaic of the parental genomes.The fixed variation in RILs is used of for fine mapping of complex traits.Cultivated diploid A genome species of cotton holds special significance to dissect complexity of a developing cotton fibers.We have evaluated the interspecifc population (Gossypium arboreum var.

  14. DNA instability in replicating Huntington's disease lymphoblasts

    Directory of Open Access Journals (Sweden)

    Frati Luigi

    2009-02-01

    Full Text Available Abstract Background The expanded CAG repeat in the Huntington's disease (HD gene may display tissue-specific variability (e.g. triplet mosaicism in repeat length, the longest mutations involving mitotic (germ and glial cells and postmitotic (neurons cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths. Results Although most lymphoblastoid cell lines (88% showed little or no repeat instability even after six or more months culture, in lymphoblasts with large expansion repeats beyond 60 CAG repeats the mutation size and triplet mosaicism always increased during replication, implying that the repeat mutability for highly expanded mutations may quantitatively depend on the triplet expansion size. None of the investigated genetic factors, potentially acting in cis to the mutation, significantly influence the repeat changes. Finally, in our experiments certain drugs controlled triplet expansion in two prone-to-expand HD cell lines carrying large CAG mutations. Conclusion Our data support quantitative evidence that the inherited CAG length of expanded alleles has a major influence on somatic repeat variation. The longest triplet expansions show wide somatic variations and may offer a mechanistic model to study triplet drug-controlled instability and genetic factors influencing it.

  15. Stem cell transplantation outcomes in lymphoblastic lymphoma.

    Science.gov (United States)

    Brammer, Jonathan E; Khouri, Issa; Marin, David; Ledesma, Celina; Rondon, Gabriela; Ciurea, Stefan O; Nieto, Yago; Champlin, Richard E; Hosing, Chitra; Kebriaei, Partow

    2017-02-01

    Lymphoblastic lymphoma (LBL) is an aggressive lymphoma pathologically similar to lymphoblastic leukemia, but primarily presents with nodal or extra-medullary involvement. The aim of this study is to describe outcomes of patients undergoing stem cell transplantation (SCT) for LBL compared to historical data. Thirty-nine patients, of which 54% lacked complete remission (CR), received SCT for LBL between 1990 and 2015; 31 allogeneic and eight autologous. Overall survival (OS) and progression free survival (PFS) at three years for the entire cohort was 41%, the cumulative incidence (CI) of non-relapse mortality (NRM) was 18% at one year, and CI relapse mortality was 28% at one-year and 36% at three years; results similar to historical reports. On multivariate analysis, the use of total-body irradiation (TBI) based conditioning and transplantation in CR were independently predictive of OS and PFS. For patients requiring SCT for LBL, CR and TBI-based conditioning prior to allogeneic SCT may provide improved disease control.

  16. Heterogeneity of DNA Distribution in Diploid Cells: A New Predicitive Discriminant Factor for Solid Tumour Behaviour

    Directory of Open Access Journals (Sweden)

    Jacques Assailly

    1999-01-01

    Full Text Available Spatial nuclear DNA heterogeneity distribution of Feulgen‐stained DNA diploid cells was studied by image cytometry in voided urine of 119 patients without bladder tumour (n=20 and with initial (n=23 or previous (n=76 diagnosed bladder tumour. For each patient, repetitive DNA measurements were performed during 1–4 years of follow up. Only cells of diploid DNA histograms and diploid subpopulations of aneuploid DNA histograms were used for analysis. DNA heterogeneity distribution of these diploid cells was quantified by statistical parameters of each nuclear optical density distribution. Discriminant analysis was performed on three groups of DNA histograms. Group A (n=44: aneuploid DNA histograms of patients with bladder tumour. Group D (n=55: 38 diploid DNA histograms of the 20 patients without bladder tumour (subgroup D1 and 17 diploid DNA histograms of patients with a non‐recurrent bladder tumour (subgroup D2. Group R (n=27: diploid DNA histograms of patients with bladder tumour recurrence. No statistically significant discriminant function was found to separate D1 and D2. However, the first canonical discriminant function C1 differentiated diploid cells of diploid DNA histograms (group D and group R from diploid cell subpopulations of aneuploid DNA histograms (group A. Mean C1 values were 1.06, 0.84 and –1.45 for groups R, D and A, respectively. The second canonical discriminant function C2 differentiated diploid DNA histograms of patients with bladder tumour recurrence (group R from diploid DNA histograms of patients without bladder tumour or without bladder tumour recurrence (group D. Mean C2 values were 1.78 and –0.76 for groups R and D, respectively. In 95% confidence limit, the rate of rediscrimination using the two first canonical discriminant functions C1 and C2 were 86.4, 74.5 and 74.1% for groups A, D and R, respectively. Percent of “grouped” cases correctly classified was 78.6%. Thus spatial DNA heterogeneity

  17. Ⅰ型登革病毒D06063株人二倍体细胞适应株的筛选及纯化%Screening and purification of Dengue-Ⅰ virus D06063 strain adapted in human diploid cells

    Institute of Scientific and Technical Information of China (English)

    赵玉娇; 潘玥; 陈俊英; 杨丽娟; 岳耀斐; 施海晶; 马绍辉; 孙强明

    2012-01-01

    目的 筛选Ⅰ型登革病毒(Dengue virus,DV)中国株D06063人胚肺二倍体细胞KMB17的适应株,经噬斑纯化后,分析其生物学特性.方法 将Ⅰ型DV中国株D06063在C6/36细胞上进行扩增,采用微量滴定法测定病毒的感染性滴度;RT-PCR法鉴定DV型别;病毒连续以4.0 MOI的量感染KMB17细胞,传代至病毒完全适应在细胞内扩增,再连续传10代,筛选出KMB17细胞适应株,并进行3轮噬斑纯化;免疫荧光法检测纯化病毒,电镜观察病毒颗粒的形态.结果 在C6/36细胞上扩增的Ⅰ型DV D06063株的滴度为6.0 lg CCID5o/ml,经RT-PCR可扩增出511 bp的DV特异基因和482 bp的Ⅰ型DV型特异性基因;病毒感染KMB17细胞后,可产生明显的细胞病变,至第10代,病毒的感染性滴度达峰值,为6.75 lg CCID50/ml;纯化的病毒经免疫荧光检测呈阳性,电镜观察显示病毒形态正常.结论 成功筛选出传代稳定性好、病毒扩增量高的Ⅰ型DVKMB17细胞适应株,纯化的病毒株保持了原始毒株的基本生物学特性.%Objective To screen the adaptive strain of Dengue-Ⅰ virus D06063 strain (China strain) in human diploid KMB17 cells, subject to plaque purification and analyze its biological characteristics. Methods Dengue- I virus D06063 strain was propagated in C6/36 cells, determined for infectious titer by microtitration, and identified for type by RT-PCR, then subcultured in KMB17 cells at a MOI of 4. 0 till the virus was completely adapted to propagation in cell, and further subcultured for 10 passages. The adapted strain was screened and subjected to three rounds of plaque purification. The purified strain was analyzed by IFA and observed for morphology of virus particles by electron microscopy. Results The Dengue- I virus D06063 strain propagated in C6/36 cells reached a titer of 6. 0 lgCCID50/ml, from which the Dengue virus (DV) specific gene at a length of 511 bp, and DV type Ⅰ specific gene at a length of 482 bp were amplified by

  18. Significant anti-proliferation of human acute lymphoblastic leukemia cells by combined treatment with chloroquine and dexamethasone%氯喹对地塞米松抑制急性淋巴细胞白血病细胞增殖的促进作用

    Institute of Scientific and Technical Information of China (English)

    周越菡; 赵关关; 杜敏; 吴宗锴; 段小群

    2014-01-01

    目的:研究氯喹对地塞米松抑制急性淋巴细胞白血病细胞增殖的促进作用及其机制。方法:采用CCK-8实验观察氯喹对地塞米松抑制人急性淋巴细胞白血病细胞株CEM-C1增殖的促进作用,并采用Western blot-ting、实时定量PCR和LysoTracker Red溶酶体染色法验证此种促进作用的机制。结果:氯喹与地塞米松合用对CEM-C1细胞增殖的抑制明显高于正常对照组(P<0.01)。氯喹与地塞米松联用上调糖皮质激素受体(GR)的蛋白质水平并抑制溶酶体功能,而溶酶体抑制剂bafilomycin A1亦可上调GR的蛋白质水平。结论:氯喹与地塞米松联用通过溶酶体介导的机制发挥抑制急性淋巴细胞白血病细胞增殖的作用。%AIM:To explore the promoting action of chloroquine on the anti-proliferation effect of dexametha-sone on acute lymphoblastic leukemia cells .METHODS:CCK-8 assay was used to assess the viability of the dexametha-sone-resistant human acute lymphoblastic leukemia CEM-C1 cell line treated with the combination of chloroquine and dexa-methasone .Western blotting , quantitative real-time PCR and LysoTracker Red staining were utilized to examine the mecha-nism.RESULTS:Combination of chloroquine and dexamethasone significantly inhibited the proliferation of CEM -C1 cells compared with control group (P<0.01).The combination of chloroquine and dexamethasone increased the abundance of glucocorticoid receptor and inhibited lysosomal function , while lysosomal inhibitor bafilomycin A 1 also increased glucocorti-coid signaling .CONCLUSION:Dexamethasone combined with chloroquine triggers an anti-proliferation effect on CEM-C1 cells via a lysosome-mediated pathway .

  19. Diploid-triploid mosaicism and tissue ploidy diversity within Platemys platycephala from Suriname.

    Science.gov (United States)

    Bickham, J W; Hanks, B G

    2009-01-01

    The twist-necked turtle, Platemys platycephala, is 1 of only 2 known species to possess sexual reproduction and diploid-triploid mosaicism. Previous studies have shown that mosaics occur in Suriname and French Guiana but only diploids are known from Bolivia and Brazil. In this paper, the frequency of ploidy mosaicism was studied in a large sample of P. platycephala from Suriname to more fully explore the diversity of ploidy levels within and among individuals. Flow-cytometric analysis of blood revealed a wide diversity of conditions including diploids, diploid-triploid mosaics, triploids, and triploid-tetraploid mosaics. The largest frequency class was 100% diploid, and the second largest was 100% triploid. However, mosaic individuals were observed from the entire spectrum of mixtures ranging from nearly all-diploid to nearly all-triploid and 2 individuals were triploid-tetraploid mosaics. It appears likely that diploids, triploids and mosaics do not represent distinct biotypes, but simply different conditions within a spectrum of possible ploidy mixtures. Studies of multiple tissues from 5 individuals showed blood alone is a good indicator of ploidy, but subtle differences were found among tissues for some individuals, and some individuals that were all-diploid or all-triploid in blood were found to be mosaic in other tissues. Triploidy was statistically associated with males, and we hypothesize that genome size plays a role in sex determination in this species.

  20. Meiotic recombination in sexual diploid and apomictic triploid dandelions (Taraxacum officinale L.)

    NARCIS (Netherlands)

    Baarlen, van P.; Dijk, van P.J.; Hoekstra, R.F.; Jong, de J.H.

    2000-01-01

    Taraxacum officinale L. (dandelion) is a vigorous weed in Europe with diploid sexual populations in the southern regions and partially overlapping populations of diploid sexuals and triploid or tetraploid apomicts in the central and northern regions. Previous studies have demonstrated unexpectedly

  1. Generation of diploid Pichia pastoris strains by mating and their application for recombinant protein production

    Directory of Open Access Journals (Sweden)

    Chen Ming-Tang

    2012-07-01

    Full Text Available Abstract Background Yeast mating provides an efficient means for strain and library construction. However, biotechnological applications of mating in the methylotrophic yeast Pichia pastoris have been hampered because of concerns about strain stability of P. pastoris diploids. The aim of the study reported here is to investigate heterologous protein expression in diploid P. pastoris strains and to evaluate diploid strain stability using high cell density fermentation processes. Results By using a monoclonal antibody as a target protein, we demonstrate that recombinant protein production in both wild-type and glycoengineered P. pastoris diploids is stable and efficient during a nutrient rich shake flask cultivation. When diploid strains were cultivated under bioreactor conditions, sporulation was observed. Nevertheless, both wild-type and glycoengineered P. pastoris diploids showed robust productivity and secreted recombinant antibody of high quality. Specifically, the yeast culture maintained a diploid state for 240 h post-induction phase while protein titer and N-linked glycosylation profiles were comparable to that of a haploid strain expressing the same antibody. As an application of mating, we also constructed an antibody display library and used mating to generate novel full-length antibody sequences. Conclusions To the best of our knowledge, this study reports for the first time a comprehensive characterization of recombinant protein expression and fermentation using diploid P. pastoris strains. Data presented here support the use of mating for various applications including strain consolidation, variable-region glycosylation antibody display library, and process optimization.

  2. Meiotic recombination in sexual diploid and apomictic triploid dandelions (Taraxacum officinale L.)

    NARCIS (Netherlands)

    Van Baarlen, P.; Van Dijk, P.J.; Hoekstra, R.F.; De Jong, J.H.

    2000-01-01

    Taraxacum officinale L. (dandelion) is a vigorous weed in Europe with diploid sexual populations in the southern regions and partially overlapping populations of diploid sexuals and triploid or tetraploid apomicts in the central and northern regions. Previous studies have demonstrated unexpectedly h

  3. Comparison between diploid and tetraploid citrus rootstocks: morphological characterization and growth evaluation

    Directory of Open Access Journals (Sweden)

    Divanilde Guerra

    2014-03-01

    Full Text Available Tetraploid citrus rootstocks may present different morphological characteristics and growth when compared to diploid ones. This worked aimed at comparing morphological characteristics and height growth of diploid and tetraploid plants from the rootstocks 'Swingle' citrumelo [C. paradise Macf. x Poncirus trifoliate (L. Raf], citrange 'Troyer' (C. sinensis (L. Osb. x P. trifoliata and citranges 'Fepagro C 13' and 'Fepagro C 37' [C. sinensis cv. Pêra x P. trifoliata] during twelve months. Diploid (2n=18 and tetraploid (2n=36 plants originated from the same seed were identified, cultivated and evaluated every 45 days regarding color, height, petiole length, leaf length and central leaflet width. Significant differences were observed for the evaluated characteristics: the average of petiole length was 1.78 cm in the diploid and 0.99 cm in the tetraploid plants; the average of leaf length was 2.32 cm in the diploid and 2.95 cm in the tetraploid plants; the average of central leaflet width was 1.33 cm in the diploid and 1.69 cm in the tetraploid plants. Moreover, tetraploid plants had darker and thicker leaves than the diploid ones. Variation regarding height was observed and the diploid plants presented higher growth than the tetraploid ones. As tetraploid plants are smaller, have a slow height growth and wider and longer leaves.

  4. The development and phenotyping of diploid recombinant inbred lines of potato

    Science.gov (United States)

    Progress continues to be made in the effort to transform potato from a tetraploid outbreeding crop into a diploid inbreeding one. This transformation will ultimately lead to more efficient breeding and cultivar development. A variety of genetic resources will be required before a cultivated diploid ...

  5. Establishment of the diploid gynogenetic hybrid clonal line of red crucian carp × common carp

    Institute of Scientific and Technical Information of China (English)

    LIU ShaoJun; DUAN Wei; TAO Min; ZHANG Chun; SUN YuanDong; SHEN JiaMin; WANG Jing; LUO KaiKun; LIU Yun

    2007-01-01

    This study investigated the gynogenetic cytobiological behavior of the third gynogenetic generation (G3), which was generated from the diploid eggs produced by the second gynogenetic generation (G2)of red crucian carp × common carp, and determined the chromosomal numbers of G3, G2×scatter scale carp and G2×allotetraploid hybrids of red crucian carp × common carp. The results showed that the diploid eggs of G2 with 100 chromosomes, activated by UV-irradiated sperm from scatter scale carp and without the treatment for doubling the chromosomes, could develop into G3 with 100 chromosomes.Similar to the first and second gynogenetic generations (G1 and G2), G3 was also diploid (2n=100) and presented the hybrid traits. The triploids (3n=150) and tetraploids (4n=200) were produced by crossing G2 with scatter scale carp, and crossing G2 with allotetraploids, respectively. The extrusion of the second polar body in the eggs of G2 ruled out the possibility that the retention of the second polar body led to the formation of the diploid eggs. In addition, we discussed the mechanism of the formation of the diploid eggs generated by G2. The establishment of the diploid gynogenesis clonal line (G1, G2 and G3) provided the evidence that the diploid eggs were able to develop into a new diploid hybrid clonal line by gynogenesis. By producing the diploid eggs as a unique reproductive way, the diploid gynogenetic progeny of allotetrapioid hybrids of red crucian carp × common carp had important significances in both biological evolution and production application.

  6. Establishment of the diploid gynogenetic hybrid clonal line of red crucian carp × common carp

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This study investigated the gynogenetic cytobiological behavior of the third gynogenetic generation (G3), which was generated from the diploid eggs produced by the second gynogenetic generation (G2) of red crucian carp × common carp, and determined the chromosomal numbers of G3, G2×scatter scale carp and G2×allotetraploid hybrids of red crucian carp × common carp. The results showed that the diploid eggs of G2 with 100 chromosomes, activated by UV-irradiated sperm from scatter scale carp and without the treatment for doubling the chromosomes, could develop into G3 with 100 chromosomes. Similar to the first and second gynogenetic generations (G1 and G2), G3 was also diploid (2n=100) and presented the hybrid traits. The triploids (3n=150) and tetraploids (4n=200) were produced by crossing G2 with scatter scale carp and crossing G2 with allotetraploids, respectively. The extrusion of the second polar body in the eggs of G2 ruled out the possibility that the retention of the second polar body led to the formation of the diploid eggs. In addition, we discussed the mechanism of the formation of the diploid eggs generated by G2. The establishment of the diploid gynogenesis clonal line (G1, G2 and G3) provided the evidence that the diploid eggs were able to develop into a new diploid hybrid clonal line by gynogenesis. By producing the diploid eggs as a unique reproductive way, the diploid gyno- genetic progeny of allotetraploid hybrids of red crucian carp × common carp had important signifi- cances in both biological evolution and production application.

  7. Diploidization of cucumber (Cucumis sativus L. haploids by colchicine treatment

    Directory of Open Access Journals (Sweden)

    Vesselina Nikolova

    2014-02-01

    Full Text Available Haploid cucumber plants are totally infertile and do not undergo spontaneous diploidization. The use of haploids depends on the possibility of doubling the chromosome number and the obtaining of stable doubled haploids (DH. Four haploids of different genotypes propagated vegetatively were treated with colchicine in order to obtain DH. The following procedures were used: 1 apical shoot meristem treatment, 2 soaking of shoot explants, 3 placing of shoot explants on medium with colchicine. Plants of the C1 generation were evaluated in respect to morphological and cytological characters and fertility. The best result of 20.9% DH was obtained after repeated treatment of the meristem with colchicine. A large group of chimeras (28.5% was also distinguished as were haploids and tetraploids. DH plants were fertile and gave uniform progeny. Chimeras had a decreased fertility and showed disturbances in meiotic divisions.

  8. The YH database: the first Asian diploid genome database

    DEFF Research Database (Denmark)

    Li, Guoqing; Ma, Lijia; Song, Chao

    2009-01-01

    The YH database is a server that allows the user to easily browse and download data from the first Asian diploid genome. The aim of this platform is to facilitate the study of this Asian genome and to enable improved organization and presentation large-scale personal genome data. Powered by GBrowse......, we illustrate here the genome sequences, SNPs, and sequencing reads in the MapView. The relationships between phenotype and genotype can be searched by location, dbSNP ID, HGMD ID, gene symbol and disease name. A BLAST web service is also provided for the purpose of aligning query sequence against YH...... genome consensus. The YH database is currently one of the three personal genome database, organizing the original data and analysis results in a user-friendly interface, which is an endeavor to achieve fundamental goals for establishing personal medicine. The database is available at http://yh.genomics.org.cn....

  9. Artificial induction of androgenetic diploid in Yellow catfish (Pelteobagrus fulvidraco)

    Institute of Scientific and Technical Information of China (English)

    XU Hui; FAN Zhaoting; CHEN Weixing; FANG Jingjie

    2007-01-01

    Androgenesis was the especial zoogamy that the germ plasma of offspring was from the agnate. In this study the eggs of Yellow catfish (Pelteobagrus fulvidraco) were irradiated by UV suspending in the synthetic ovarian fluid (OF), and the total dosage of UV irradiation was 220 mJ·cm-2. Diploid could be induced by heat shock (40℃, 2 min, 3 min) with different time period after fertilization (15-37 min). The result showed that heat shock with 2 min was better than 3 min; there were two apices of induction in 17-21 min and 27-31 min after fertilization. The highest hatching rate was 3.30% at 29 min after fertilization, and the difference between two apices of induction was unobvious.

  10. The YH database: the first Asian diploid genome database.

    Science.gov (United States)

    Li, Guoqing; Ma, Lijia; Song, Chao; Yang, Zhentao; Wang, Xiulan; Huang, Hui; Li, Yingrui; Li, Ruiqiang; Zhang, Xiuqing; Yang, Huanming; Wang, Jian; Wang, Jun

    2009-01-01

    The YH database is a server that allows the user to easily browse and download data from the first Asian diploid genome. The aim of this platform is to facilitate the study of this Asian genome and to enable improved organization and presentation large-scale personal genome data. Powered by GBrowse, we illustrate here the genome sequences, SNPs, and sequencing reads in the MapView. The relationships between phenotype and genotype can be searched by location, dbSNP ID, HGMD ID, gene symbol and disease name. A BLAST web service is also provided for the purpose of aligning query sequence against YH genome consensus. The YH database is currently one of the three personal genome database, organizing the original data and analysis results in a user-friendly interface, which is an endeavor to achieve fundamental goals for establishing personal medicine. The database is available at http://yh.genomics.org.cn.

  11. A fast and accurate algorithm for diploid individual haplotype reconstruction.

    Science.gov (United States)

    Wu, Jingli; Liang, Binbin

    2013-08-01

    Haplotypes can provide significant information in many research fields, including molecular biology and medical therapy. However, haplotyping is much more difficult than genotyping by using only biological techniques. With the development of sequencing technologies, it becomes possible to obtain haplotypes by combining sequence fragments. The haplotype reconstruction problem of diploid individual has received considerable attention in recent years. It assembles the two haplotypes for a chromosome given the collection of fragments coming from the two haplotypes. Fragment errors significantly increase the difficulty of the problem, and which has been shown to be NP-hard. In this paper, a fast and accurate algorithm, named FAHR, is proposed for haplotyping a single diploid individual. Algorithm FAHR reconstructs the SNP sites of a pair of haplotypes one after another. The SNP fragments that cover some SNP site are partitioned into two groups according to the alleles of the corresponding SNP site, and the SNP values of the pair of haplotypes are ascertained by using the fragments in the group that contains more SNP fragments. The experimental comparisons were conducted among the FAHR, the Fast Hare and the DGS algorithms by using the haplotypes on chromosome 1 of 60 individuals in CEPH samples, which were released by the International HapMap Project. Experimental results under different parameter settings indicate that the reconstruction rate of the FAHR algorithm is higher than those of the Fast Hare and the DGS algorithms, and the running time of the FAHR algorithm is shorter than those of the Fast Hare and the DGS algorithms. Moreover, the FAHR algorithm has high efficiency even for the reconstruction of long haplotypes and is very practical for realistic applications.

  12. Acute lymphoblastic leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available on the Trial E.1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute... lymphoblastic leukemia E.1.1.1Medical condition in easily understood language Acute lymphoblastic

  13. Identification and cloning of a prethymic precursor T lymphocyte from a population of common acute lymphoblastic leukemia antigen (CALLA)-positive fetal bone marrow cells

    DEFF Research Database (Denmark)

    Hokland, P; Hokland, M; Daley, J

    1987-01-01

    We have cloned common acute lymphoblastic leukemia (CALLA)-positive cells from human fetal bone marrow containing less than 1 in 10,000 E-RFC in round-bottomed microtiter wells (one cell per well) using the autocloning unit of an EPICS-V cell sorter. Expansion of such cells (with IL-2 and heavily...

  14. Resveratrol given intraperitoneally does not inhibit growth of high-risk t(4;11) acute lymphoblastic leukemia cells in NOD/SCID mouse model

    Science.gov (United States)

    The efficacy of the phytochemical resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL line SEM. SEM cells were injected into the tail vein and engraftment was monitored by ...

  15. Chromosome doubling in early spermatogonia produces diploid spermatozoa in a natural clonal fish.

    Science.gov (United States)

    Yoshikawa, Hiroyuki; Morishima, Kagayaki; Fujimoto, Takafumi; Saito, Taiju; Kobayashi, Tohru; Yamaha, Etsuro; Arai, Katsutoshi

    2009-05-01

    The natural clonal loach Misgurnus anguillicaudatus (Teleostei: Cobitidae) is diploid (2n = 50) and produces genetically identical unreduced eggs, which develop into diploid individuals without any genetic contribution from sperm. Artificially sex-reversed clones created by the administration of 17alpha-methyltestosterone produce clonal diploid sperm. In metaphase spreads from testicular cells of the sex-reversed clones, spermatocytes had twice the normal number of chromosomes (50 bivalents) compared with those of normal diploids (25 bivalents). Thus, the production of unreduced diploid spermatozoa is initiated by premeiotic endomitosis (or endoreduplication), chromosome doubling before meiosis, and is followed by two quasinormal divisions. Larger nuclei in the germ cells were observed in all stages of type B spermatogonia in the testes of the sex-reversed clones. In contrast, besides having larger type A spermatogonia, the sex-reversed clones also had the type A spermatogonia that were the same size as those of normal diploids. It follows that chromosome duplication causing unreduced spermatogenesis occurred in the type A spermatogonia. The presence of tetraploid type A and early type B spermatogonia, identified by labeling with antispermatogonia-specific antigen 1, was verified using DNA content flow cytometry. These results support the conclusion that chromosome doubling occurs at the type A spermatogonial stage in diploid spermatogenesis in the clonal fish.

  16. Nucleotide sequencing of hepatitis A virus Js-4 strain subcultured in human diploid cells%甲型肝炎病毒Js-4株经人二倍体细胞传代后的核苷酸序列分析

    Institute of Scientific and Technical Information of China (English)

    胡艳灵; 陈统球; 黄明; 戚凤春; 崔燕萍; 潘翔

    2012-01-01

    目的 分析甲型肝炎病毒(Hepatitis A virus,HAV)Js-4株经人二倍体细胞MRC-5传代后的核苷酸序列变异情况.方法 将HAV Js-4株经Vero细胞适应14代获得的原始株Js-4-V14经人二倍体细胞MRC-5于35℃连续适应培养15代,取其中8个适应株(Js-4-M2、Js-4-M3、Js-4-M4、Js-4-M5、Js-4-M10、Js-4-M12、Js-4-M14、Js-4-M15)及原始株,提取病毒基因组RNA,通过RTPCR扩增病毒全基因组,采用生物信息学软件DNAstar Lasergene 7进行序列分析.结果 8个适应株全基因组与Js-4-V14株的核苷酸序列同源性在99.8%~100.0%之间;第5代适应株在5′-NCR(101~ 200 bp)发生较大变异,表现为105~157bp缺失,之后该突变稳定遗传;第10、12、14、15代适应株在2A(3 012 ~3 210 bp)区段3 122位点发生点突变;8个适应株和Js-4-V14毒株与野毒株HM175为同一基因亚型,均为IB型;9个毒株的主要抗原位点与野生株HM175完全一致.结论 HAV Js-4-V14株在MRC-5细胞传代适应过程中,主要抗原位点未发生突变,其与细胞适应性和病毒增殖有关的基因在传代早期已经变异,传代后期这些变异保持相对稳定.%Objective To analyze the variation of nucleotide sequence of hepatitis A virus (HAV) Js-4 strain after subculture in human diploid MRC-5 cells. Methods HAV Js-4 strain was subcultured in Vero cells for 14 passages, and the obtained Js-4-V14 strain was inoculated to MRC-5 cells and further subcultured at 35 Xl for 15 passages. Genomic RNAs were extracted from Js-4-V14 strain as well as eight adapted strains, i. e. Js-4-M2, Js-4-M3, Js-4-M4, Js-4-M5, Js-4-M10, Js-4-Mu, Js-4-M14 and Js-4-Mi5, with which the whole genomes were amplified by RT-PCR and sequenced by bioinformatics software DNAstar Lasergene 1. Results The homologies of whole genomes of eight adapted strains to those of strain Js-4-V14 were 99. 8% ~ 100. 0%. However, obvious variation was observed in 5'-NCR (101 ~ 200 bp) of strain Js-4-M5, expressed as deletion

  17. Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-12-28

    B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; BCR-ABL1 Fusion Protein Expression; Minimal Residual Disease; Philadelphia Chromosome Positive; T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  18. Molecular Characterization of Banana (AA Diploids with Contrasting Levels of Black and Yellow Sigatoka Resistance

    Directory of Open Access Journals (Sweden)

    Claudia F. Ferreira

    2004-01-01

    Full Text Available Most banana cultivars are susceptible to many diseases, whereas Sigatoka leads to greatest yield losses. One of the strategies to overcome this disease is thorough banana genetic breeding which consists in the obtainment of improved (AA diploids which are then crossed with triploids obtaining (AAAB tetraploid disease resistant bananas also presenting other important agronomic characteristics. The prior knowledge of the genetic diversity of (AA diploids, is therefore considered indispensable in order to direct the crosses being made. The objective of the present work was to analyze the genetic diversity of 20 (AA banana diploids with contrasting levels of reaction to yellow and black Sigatoka caused by Mycosphaerella musicola and M. fijensis, respectively, using molecular markers. From the dendrogram data it is shown that a great number of experimental hybrids can be obtained from the combination of genetically different diploids, therefore making the banana genetic breeding program more efficient regarding its objectives.

  19. Diploid and tetraploid grey treefrogs (Hyla chrysoscelis and Hyla versicolor) have similar metabolic rates.

    Science.gov (United States)

    Kamel, S; Marsden, J E; Pough, F H

    1985-01-01

    We measured oxygen consumption of the diploid frog Hyla chrysoscelis and its recently evolved tetraploid cryptic species Hyla versicolor at rest and during forced locomotory exercise. We also measured whole-body lactic acid concentrations of individuals of the two species at rest and following 4 min of exercise. Contrary to predictions based on tissue-culture experiments, rates of organismal metabolism are not different in this diploid/tetraploid species pair: the diploid and tetraploid species did not differ in rates of oxygen consumption at rest or during exercise. Furthermore, whole-body lactate concentrations of frogs at rest and following forced locomotion were the same in the diploid and tetraploid species. For these species, polyploidy does not appear to be associated with lower maintenance costs at the level of the organism. However, polyploidy also does not appear to have metabolic consequences that would limit the behavioral or ecological repertoire of an anuran.

  20. Characterization of a heteropolysaccharide isolated from diploid Gynostemma pentaphyllum Makino.

    Science.gov (United States)

    Yan, Wei; Niu, Yuge; Lv, Junli; Xie, Zhuohong; Jin, Lei; Yao, Wenbing; Gao, Xiangdong; Yu, Liangli Lucy

    2013-02-15

    A novel water-soluble polysaccharide (GPP), with a molecular mass of 7.1×10(3) Da, was isolated from the defatted whole-plant of diploid Gynostemma pentaphyllum Makino. Monosaccharide composition analysis indicated that GPP was a heteropolysaccharide mainly containing mannose, glucose, galactose and arabinose, at a molar ratio of 1.00:77.33:4.81:1.83. The detailed structure analysis revealed that GPP consisted of a (1→4)-α-D-glucoside backbone with a 1→)-α-D-glucopyranosyl branch at the C-6 position of (1→4,6)-linked-α-D-glucopyranosyl on every 5 monosaccharide residues, with a few mannose, galactose and arabinose terminal residues. GPP exhibited scavenging capacities against hydroxyl, peroxyl and DPPH radicals in vitro, and had a greater bile acid-binding ability than psyllium on a per weight basis. These results suggested a potential application of GPP in functional foods and dietary supplements. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Diploid Male Production of Two Amazonian Melipona Bees (Hymenoptera: Apidae

    Directory of Open Access Journals (Sweden)

    Izaura Bezerra Francini

    2012-01-01

    Full Text Available The diploid male has already been recorded for Melipona Illger, and herein, in Melipona seminigra merrillae Cockerell and Melipona interrupta manaosensis Schwarz. This paper was carried out at the Instituto Nacional de Pesquisas da Amazônia (INPA, Manaus, AM, Brazil. We produced and monitored 31 new colonies of M. s. merrillae and 32 new colonies of M. i. manaosensis. We sampled 2,995 pupae of M. s. merrillae and 2,020 of M. i. manaosensis. In colonies with a 1 : 1 sex ratio, male diploidy was confirmed by cytogenetic analysis and workers’ behavior. We estimated 16 sex-determining alleles in M. s. merrillae and 22 in M. i. manaosensis. In colonies of M. i. manaosensis in a 1 : 1 sex ratio, workers killed the males and the queen that produced them soon after they emerged, as predicted. This behavior was not registered for M. s. merrillae, and sex ratios did not stay 1 : 1, indicating polyandry for this species.

  2. Insights into the Evolution of Cotton Diploids and Polyploids from Whole-Genome Re-sequencing

    OpenAIRE

    Page, Justin T.; Huynh, Mark D; Zach S Liechty; Grupp, Kara; Stelly, David; Hulse, Amanda M; Ashrafi, Hamid; Van Deynze, Allen; Wendel, Jonathan F.; Udall, Joshua A.

    2013-01-01

    Understanding the composition, evolution, and function of the Gossypium hirsutum (cotton) genome is complicated by the joint presence of two genomes in its nucleus (AT and DT genomes). These two genomes were derived from progenitor A-genome and D-genome diploids involved in ancestral allopolyploidization. To better understand the allopolyploid genome, we re-sequenced the genomes of extant diploid relatives that contain the A1 (Gossypium herbaceum), A2 (Gossypium arboreum), or D5 (Gossypium ra...

  3. Diploid and triploid African catfish (Clarias gariepinus) differ in biomarker responses to the pesticide chlorpyrifos.

    Science.gov (United States)

    Karami, Ali; Goh, Yong-Meng; Jahromi, Mohammad Faseleh; Lazorchak, James M; Abdullah, Maha; Courtenay, Simon C

    2016-07-01

    The impacts of environmental stressors on polyploid organisms are largely unknown. This study investigated changes in morphometric, molecular, and biochemical parameters in full-sibling diploid and triploid African catfish (Clarias gariepinus) in response to chlorpyrifos (CPF) exposures. Juvenile fish were exposed to three concentrations of CPF (mean measured μg/L (SD): 9.71 (2.27), 15.7 (3.69), 31.21 (5.04)) under a static-renewal condition for 21days. Diploid control groups had higher hepatosomatic index (HSI), plasma testosterone (T), and brain GnRH and cyp19a2 expression levels than triploids. In CPF-exposed groups, changes in HSI, total weight and length were different between the diploid and triploid fish. In contrast, condition factor did not alter in any of the treatments, while visceral-somatic index (VSI) changed only in diploids. In diploid fish, exposure to CPF did not change brain 11β-hsd2, ftz-f1, foxl2, GnRH or cyp19a2 mRNA levels, while reduced tph2 transcript levels compared to the control group. In contrast, 11β-hsd2 and foxl2 expression levels were changed in triploids following CPF exposures. In diploids, plasma T levels showed a linear dose-response reduction across CPF treatments correlating with liver weight and plasma total cholesterol concentrations. In contrast, no changes in plasma cholesterol and T concentrations were observed in triploids. Plasma cortisol and 17-β estradiol (E2) showed no response to CPF exposure in either ploidy. Results of this first comparison of biomarker responses to pesticide exposure in diploid and polyploid animals showed substantial differences between diploid and triploid C. gariepinus.

  4. Treatment of adult acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jacobs, P; Wood, L; Novitzky, N

    1990-01-01

    Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

  5. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

    Science.gov (United States)

    Yang, Jun J.; Hunger, Stephen P.; Pieters, Rob; Schrappe, Martin; Biondi, Andrea; Vora, Ajay; Baruchel, André; Silverman, Lewis B.; Schmiegelow, Kjeld; Escherich, Gabriele; Horibe, Keizo; Benoit, Yves C.M.; Izraeli, Shai; Yeoh, Allen Eng Juh; Liang, Der-Cherng; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.

    2015-01-01

    Purpose To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. PMID:26304874

  6. The evolutionary advantage of haploid versus diploid microbes in nutrient-poor environments.

    Science.gov (United States)

    Bessho, Kazuhiro; Iwasa, Yoh; Day, Troy

    2015-10-21

    Sexual eukaryotic organisms are characterized by haploid and diploid nuclear phases. In many organisms, growth and development occur in both haploid and diploid phases, and the relative length of these phases exhibits considerable diversity. A number of hypotheses have been put forward to explain the maintenance of this diversity of life cycles and the advantage of being haploid versus that of being diploid. The nutrient-limitation hypothesis postulates that haploid cells, because they are small and thus have a higher surface area to volume ratio, are advantageous in nutrient-poor environments. In this paper, we examine this hypothesis theoretically and determine the conditions under which it holds. On the basis of our analysis, we make the following predictions. First, the relative advantages of different ploidy levels strongly depend on the ploidy-dependent energy conversion efficiency and the scaling of mortality with cell size. Specifically, haploids enjoy a higher intrinsic population growth rate than diploids do under nutrient-poor conditions, but under nutrient-rich conditions the intrinsic population growth rate of diploids is higher, provided that the energy conversion efficiency of diploids is higher than that of haploids and the scaling of mortality with cell size is weak. Second, differences in nutrient concentration in the inflowing medium have almost no effect on the relative advantage of ploidy levels at population equilibrium. Our study illustrates the importance of explicit modeling of microbial life history and population dynamics to understand the evolution of ploidy levels.

  7. Somatic cell nuclear transfer: infinite reproduction of a unique diploid genome.

    Science.gov (United States)

    Kishigami, Satoshi; Wakayama, Sayaka; Hosoi, Yoshihiko; Iritani, Akira; Wakayama, Teruhiko

    2008-06-10

    In mammals, a diploid genome of an individual following fertilization of an egg and a spermatozoon is unique and irreproducible. This implies that the generated unique diploid genome is doomed with the individual ending. Even as cultured cells from the individual, they cannot normally proliferate in perpetuity because of the "Hayflick limit". However, Dolly, the sheep cloned from an adult mammary gland cell, changes this scenario. Somatic cell nuclear transfer (SCNT) enables us to produce offspring without germ cells, that is, to "passage" a unique diploid genome. Animal cloning has also proven to be a powerful research tool for reprogramming in many mammals, notably mouse and cow. The mechanism underlying reprogramming, however, remains largely unknown and, animal cloning has been inefficient as a result. More momentously, in addition to abortion and fetal mortality, some cloned animals display possible premature aging phenotypes including early death and short telomere lengths. Under these inauspicious conditions, is it really possible for SCNT to preserve a diploid genome? Delightfully, in mouse and recently in primate, using SCNT we can produce nuclear transfer ES cells (ntES) more efficiently, which can preserve the eternal lifespan for the "passage" of a unique diploid genome. Further, new somatic cloning technique using histone-deacetylase inhibitors has been developed which can significantly increase the previous cloning rates two to six times. Here, we introduce SCNT and its value as a preservation tool for a diploid genome while reviewing aging of cloned animals on cellular and individual levels.

  8. Tetraploid somatic hybrids of potato (Solanum tuberosum L.) obtained from diploid breeding lines.

    Science.gov (United States)

    Przetakiewicz, Jarosław; Nadolska-Orczyk, Anna; Kuć, Dominik; Orczyk, Wacław

    2007-01-01

    Intraspecific somatic hybrids between 16 different diploid breeding lines of Solanum tuberosum L. were produced by PEG-induced fusion. Manually selected heterokaryons were cultured in a Millicells-CM using a post-fusion protoplast mixture. Plants were regenerated from calli derived from heterokaryons obtained from 10 out of 38 combinations of diploid lines. Of the tested putative somatic hybrids, 14.2% were diploid, 72.8% were tetraploid and 13% pentaploid. The DNA amplification pattern obtained with RAPD or semi-random primers confirmed that 6 fusion combinations were hybrids. In most cases, the morphological traits were intermediate to those of the diploid fusion partners. About 23.0% of the tested somatic hybrids showed variation in their morphology. Of the tested somatic hybrids, 78.0% flowered and 86.0% tuberized. The cytoplasm of 9 diploid lines and 6 somatic hybrid combinations was analysed. Two of the diploid lines had W/S chloroplasts and alpha or epsilon mitochondria; the remainder contained T chloroplasts and beta mitochondria. All the analysed somatic hybrids carried T chloroplasts and beta mitochondria.

  9. Aspects of gene regulation in the diploid and tetraploid Odontophrynus americanus (Amphibia, Anura, Leptodactylidae

    Directory of Open Access Journals (Sweden)

    Cianciarullo Aurora M.

    2000-01-01

    Full Text Available Erythropoietic and hemoglobin DNA transcriptional activities were analyzed in the diploid and the tetraploid Odontophrynus americanus. Flow cytometric analyses of DNA, RNA and mitochondrial contents showed increased genic activity in both diploid and tetraploid animals during erythropoiesis in vivo elicited by pretreatment phenylhydrazine. Generally, higher values were seen in immature tetraploid erythroid cells. On the 10th day of recovery from anemia, large amounts of messenger RNA were found in both specimens. Based on the mitochondrial content, the tetraploid cells had more intense energy metabolism than the diploid cells. Diploid O. americanus had about three times more erythroid cells than tetraploid specimens, indicating that there were differences in the regulatory mechanisms of erythroid cells. Hematological parameters showed that tetraploid cells had 30% more hemoglobin than the diploid, suggesting a regulatory mechanism of hemoglobin synthesis at the transcriptional level. Cytoplasmic inclusions resembling Heinz bodies were found in both types of cells. In the tetraploid cells they were previously found associated with RNA or RNP, suggesting that other regulatory system which controls the accumulation of nontranslated RNA transcribed in excess must be present. These differences at the physiological and molecular levels during erythropoiesis reinforce the hypothesis that speciation is occurring between diploid and tetraploid O. americanus.

  10. [Effects of Sam68 gene silence on proliferation of acute T lymphoblastic leukemia cell line Jurkat].

    Science.gov (United States)

    Wang, Chi-Juan; Xu, Hua; Zhang, Hai-Rui; Wang, Jian; Lin, Ya-Ni; Pang, Tian-Xiang; Li, Qing-Hua

    2014-08-01

    This study was purpose to investigate the effect of Sam68 gene silence on proliferation of human acute T lymphoblastic leukemia cell line Jurkat. The sequence of shRNA targeting the site 531-552 of Sam68 mRNA was designed and chemically synthesized, then a single-vector lentiviral, Tet-inducible shRNA-Sam68 system (pLKO-Tet-On) was constructed; next the Jurkat cells were infected with lentivirus to create stable cell clones with regulatable Sam68 gene expression. The inhibitory efficiency of Sam68 gene was assayed by Real-time PCR and Western blot; the cell activity of Jurkat cells was detected with MTT assay; the change of colony forming potential of Jurkat cells was analyzed by colony forming test; the cell cycle distribution was tested by flow cytometry. The results indicated that the expression of Sam68 in experimental cells was statistically decreased as compared with that of the control cells; the cells activity and colony forming capacity of the Jurkat cells with Sam68 gene silence were significantly inhibited; with Sam68 gene silencing, the percentage of S phase cells was significantly increased, while the percentage of G2 phase cells was significantly decreased. It is concluded that the silencing Sam68 gene using shRNA interference can effectively inhibit the proliferation of human acute T lymphoblastic leukemia cell line Jurkat.

  11. Acute lymphoblastic leukemia in adolescents and young adults in Finland.

    Science.gov (United States)

    Usvasalo, Anu; Räty, Riikka; Knuutila, Sakari; Vettenranta, Kim; Harila-Saari, Arja; Jantunen, Esa; Kauppila, Marjut; Koistinen, Pirjo; Parto, Katriina; Riikonen, Pekka; Salmi, Toivo T; Silvennoinen, Raija; Elonen, Erkki; Saarinen-Pihkala, Ulla M

    2008-08-01

    Interest has recently been paid to adolescents and young adults with acute lymphoblastic leukemia, particularly because all reports so far published indicate that these patients have a better outcome when treated with pediatric rather than adult therapeutic protocols. There are different biological subtypes of acute lymphoblastic leukemia with distinct features and prognoses; the distribution of these subtypes is not well known among adolescents. We, therefore, studied acute lymphoblastic leukemia in adolescents and young adults aged 10 to 25 years in Finland. This population-based study included 225 consecutive patients aged 10-25 years diagnosed with acute lymphoblastic leukemia during 1990-2004. One hundred and twenty-eight patients (10-16 years) were treated with pediatric Nordic (NOPHO) protocols, and 97 patients (17-25 years) with Finnish Leukemia Group National protocols. We characterized the biological subtypes, clinical features and outcome of these patients. For the whole cohort, the remission rate was 96%, 5-year event-free survival 62% and overall survival 72%. The 5-year event-free survival was 67% for the pediatric treatment group and 60% for the adult treatment group (p=n.s.). Patients with inferior outcome were those with a white blood cell count >or= 100 x 10(9)/L, the Philadelphia chromosome and MLL. Good prognostic features were TEL-AML1, hyperdiploidy, and pediatric intermediate risk stratification. Unlike all previous studies, we found that the outcome of adolescents and young adults with acute lymphoblastic leukemia treated with pediatric or adult therapeutic protocols was comparable. The success of the adult acute lymphoblastic leukemia therapy emphasizes the benefit of central referral of patients to academic centers and adherence to research protocols.

  12. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

  13. Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies.

    Directory of Open Access Journals (Sweden)

    Melanie Legrand

    2008-01-01

    Full Text Available Haplotype maps (HapMaps reveal underlying sequence variation and facilitate the study of recombination and genetic diversity. In general, HapMaps are produced by analysis of Single-Nucleotide Polymorphism (SNP segregation in large numbers of meiotic progeny. Candida albicans, the most common human fungal pathogen, is an obligate diploid that does not appear to undergo meiosis. Thus, standard methods for haplotype mapping cannot be used. We exploited naturally occurring aneuploid strains to determine the haplotypes of the eight chromosome pairs in the C. albicans laboratory strain SC5314 and in a clinical isolate. Comparison of the maps revealed that the clinical strain had undergone a significant amount of genome rearrangement, consisting primarily of crossover or gene conversion recombination events. SNP map haplotyping revealed that insertion and activation of the UAU1 cassette in essential and non-essential genes can result in whole chromosome aneuploidy. UAU1 is often used to construct homozygous deletions of targeted genes in C. albicans; the exact mechanism (trisomy followed by chromosome loss versus gene conversion has not been determined. UAU1 insertion into the essential ORC1 gene resulted in a large proportion of trisomic strains, while gene conversion events predominated when UAU1 was inserted into the non-essential LRO1 gene. Therefore, induced aneuploidies can be used to generate HapMaps, which are essential for analyzing genome alterations and mitotic recombination events in this clonal organism.

  14. [Alcaligenes xylosoxidans bacteremia in a patient with acute lymphoblastic leukemia].

    Science.gov (United States)

    Aydemir, Zeynep Alp; Ozdemir, Nihal; Celik, Nigar; Celkan, Tiraje

    2009-07-01

    Alcaligenes xylosoxidans which is an aerobic, non-fermentative gram-negative bacillus found in aqueous environments and human flora, can lead to opportunistic infections. It causes infections in elderly, immunocompromised patients, patients with chronic disorders or premature infants. In this report, a case of A. xylosoxidans bacteremia that developed in a child with acute lymphoblastic leukemia (ALL) was presented. Four-years-old male patient under ALL induction therapy was admitted with symptoms of lethargy, headache, somnolence, and fever (39 degrees C). Cerebrospinal fluid, blood, throat and urine cultures were taken from the patient and empirical treatment with sulbactam cefoperazon and amikacin was initiated. Blood cultures in BacT Alert 3D (Bio Merieux, France) revealed the growth of a gram-negative coccobacillus. The agent which was non-fermentative, indol and H2S negative, was identified as A. xylosoxidans by API 20 NE (Bio Merieux, France). Since fever continued under the current antibiotic treatment, the therapy was switched to imipenem (90 mg/kg 3x/day) and the patient's condition improved markedly after 24 hours. Disc diffusion susceptibility testing of the isolate revealed that it was resistant to ampicillin, cephalothin, cefuroxime, cefoxitin, cefotaxime, amikacin, netilmicin and gentamicin; susceptible to amoxicillin clavulanate, piperacillin tazobactam, seftazidime, cefepime, imipenem and ciprofloxacin. Following 14 days of imipenem therapy, the patient recovered and discharged from the hospital on routine follow-up. It is important to consider A. xylosoxidans as a possible causative agent particularly in the infections that develop in high risk patients at oncology, dialysis and neonatal intensive care units.

  15. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  16. High-Risk Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Howard, Scott C.; Pui, Ching-Hon

    2009-01-01

    Although most children with acute lymphoblastic leukemia (ALL) are cured, certain subsets have a high risk of relapse. Relapse risk can be predicted by early response to therapy, clinical and pharmacogenetic features of the host, and genetic characteristics of leukemic cells. Though early treatment response can be assessed by the peripheral blast cell count after 1 week of single-agent glucocorticoid treatment or percent of bone marrow blasts by morphology after 1 or 2 weeks of multiagent induction treatment, determination of minimal residual disease by polymerase chain reaction (PCR) or flow cytometry after 2 to 6 weeks of induction is the most precise and useful measure. Augmented therapy has improved outcome for the poor responders to initial treatment. Infants with mixed-lineage leukemia (MLL)–rearranged ALL comprise a very poor-risk group wherein further intensification of chemotherapy causes significant toxicity. Hybrid protocols incorporating drugs effective for acute myeloid leukemia could improve survival, a strategy being tested in international trials. Studies on the biology of MLL-induced leukemogenesis have prompted the development of novel targeted agents, currently under evaluation in clinical trials. Short-term outcomes of patients with Philadelphia chromosome (Ph)–positive ALL have improved significantly by adding tyrosine kinase inhibitors to standard chemotherapy regimens. New agents and methods to overcome resistance are under investigation, and allogeneic stem cell transplantation is recommended for certain subsets of patients, for example those with Ph+ and T-cell ALL with poor early response. Genome-wide interrogation of leukemic cell genetic abnormalities and germline genetic variations promise to identify new molecular targets for therapy. PMID:19778845

  17. Treatment of acute lymphoblastic leukaemia (ALL).

    Science.gov (United States)

    Jacobs, P; Wood, L

    1992-08-01

    Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

  18. Triploid Production from Interspecific Crosses of Two Diploid Perennial Helianthus with Diploid Cultivated Sunflower (Helianthus annuus L.)

    Science.gov (United States)

    Liu, Zhao; Seiler, Gerald J.; Gulya, Thomas J.; Feng, Jiuhuan; Rashid, Khalid Y.; Cai, Xiwen; Jan, Chao-Chien

    2017-01-01

    Wild Helianthus species are a valuable genetic resource for the improvement of cultivated sunflower. We report the discovery and characterization of a unique high frequency production of triploids when cultivated sunflower was pollinated by specific accessions of diploid Helianthus nuttallii T. & G. and H. maximiliani Schr. Genomic in situ hybridization (GISH) analyses indicated that the triploid F1s had two genomes from the wild pollen sources and one from the cultivated line. Mitotic chromosome analyses indicated that the frequency of triploid progenies from the crosses of cultivated lines × H. nuttallii accession 102 (N102) was significantly higher than those of unexpected polyploid progenies from the crosses of wild perennial species × N102, and no unexpected polyploids were obtained from the reverse crosses. Pollen stainability analysis suggested the existence of a low percentage of unreduced (2n) male gametes in some accessions, especially N102 and H. maximiliani accession 1113 (M1113), which were generated at the telophase II and tetrad stages of meiosis. The triploid F1s could be the results of preferred fertilization of the low frequency of 2n male gametes with the female gametes of the cultivated sunflower, due to the dosage factors related to recognition and rejection of foreign pollen during fertilization. The triploids have been used to produce amphiploids and aneuploids. Future studies of the male gametes’ fate from pollination through fertilization will further uncover the mechanism of this whole genome transmission. Studies of the genetic control of this trait will facilitate research on sunflower polyploidy speciation and evolution, and the utilization of this trait in sunflower breeding. PMID:28179393

  19. Triploid Production from Interspecific Crosses of Two Diploid Perennial Helianthus with Diploid Cultivated Sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Liu, Zhao; Seiler, Gerald J; Gulya, Thomas J; Feng, Jiuhuan; Rashid, Khalid Y; Cai, Xiwen; Jan, Chao-Chien

    2017-02-07

    Wild Helianthus species are a valuable genetic resource for the improvement of cultivated sunflower. We report the discovery and characterization of a unique high frequency production of triploids when cultivated sunflower was pollinated by specific accessions of diploid Helianthus nuttallii T. &. G. and H. maximiliani Schr. Genomic in situ hybridization (GISH) analyses indicated that the triploid F1s had two genomes from the wild pollen sources and one from the cultivated line. Mitotic chromosome analyses indicated that the frequency of triploid progenies from the crosses of cultivated lines × H. nuttallii accession 102 (N102) was significantly higher than those of unexpected polyploid progenies from the crosses of wild perennial species × N102, and no unexpected polyploids were obtained from the reverse crosses. Pollen stainability analysis suggested the existence of a low percentage of unreduced (2n) male gametes in some accessions, especially N102 and H. maximiliani accession 1113 (M1113), which were generated at the telophase II and tetrad stages of meiosis. The triploid F1s could be the results of preferred fertilization of the low frequency of 2n male gametes with the female gametes of the cultivated sunflower, due to the dosage factors related to recognition and rejection of foreign pollen during fertilization. The triploids have been used to produce amphiploids and aneuploids. Future studies of the male gametes' fate from pollination through fertilization will further uncover the mechanism of this whole genome transmission. Studies of the genetic control of this trait will facilitate research on sunflower polyploidy speciation and evolution, and the utilization of this trait in sunflower breeding.

  20. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

    Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin

    2014-01-01

    Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995...

  1. L-asparaginase treatment in acute lymphoblastic leukemia

    NARCIS (Netherlands)

    R. Pieters (Rob); S.P. Hunger (Stephen); J. Boos (Joachim); C. Rizzari (Carmelo); L.B. Silverman (Lewis); A. Baruchel (André); N. Goekbuget (Nicola); M. Schrappe (Martin); C.H. Pui (Ching-Hon)

    2011-01-01

    textabstractAsparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive a

  2. Obesity in patients with acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Iughetti Lorenzo

    2012-01-01

    Full Text Available Abstract Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

  3. Bone histomorphometry in children with newly diagnosed acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Leeuw, JA; Koudstaal, J; Wiersema-Buist, J; Kamps, WA; Timens, W

    2003-01-01

    The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with t

  4. Academic career after treatment for acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Kingma, A; Rammeloo, LAJ; van der Does-van den Berg, A; Rekers-Mombarg, L; Postma, A

    2000-01-01

    Aim-To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings. Patients-Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluati

  5. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Wolthers, Benjamin O.; Frandsen, Thomas L.; Baruchel, André

    2017-01-01

    BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing pa...

  6. Relationship between ABO blood group and Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Tavasolian, F; Abdollahi, E; Vakili, M; Amini, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) constitute a family of genetically heterogeneous lymphoid neoplasms derived from B- and T-lymphoid progenitors. ALL affects both children and adults. Diagnosis is based on morphologic, immunophenotypic, and genetic features that allow differentiation from normal progenitors and other hematopoietic and nonhematopoietic neoplasms. The aim of this study was to investigate the association between ALL and ABO blood group. This is a case-control study that was carried out in Amir Oncology Hospital in Shiraz during 2011 to2013. The case group consisted of 293 patients with acute lymphoblastic leukemia. And compared with 300 subject in control group ( the age in the case group was between 2-5 year, and the age in the control group was between 2-45 year) .Statistical analyzes was done performed by chi -square test. The results was considered significant when p value ABO blood group distribution was 82(A), 59 (B), 24 (AB) and 128(O) in patient with Acute Lymphoblastic Leukemia and the blood group of 300 participants in the control group include, 63% (25) A, 69% (25.6) B, 18 % 06.8) AB and 101% (42.6) O. The ABO blood group distribution showed that there is significant differences between ABO blood group and patients with acute lymphoblastic leukemia . This study showed significant association between ALL and ABO blood group and showed that blood group AB was associated with a higher risk of All (p value<0.001).

  7. Epigenetics in MLL-rearranged infant Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    D.J.P.M. Stumpel (Dominique)

    2012-01-01

    textabstractNowadays the cure rate for children diagnosed with acute lymphoblastic leukemia (ALL) has exceeded 80%. Although this is considered to be one of the major successes in pediatric oncology, the subgroup of patients that did not benefit from the improved therapeutic strategies should not be

  8. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Devidsen, M.L.; Dalhoff, K.; Schmiegelow, K.

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  9. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    Science.gov (United States)

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  10. Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Vestergaard, T.; Nielsen, S.M.

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis...

  11. Pharmacogenetics influence treatment efficacy in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Dalhoff, Kim; Schmiegelow, Kjeld

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  12. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  13. Nucleostemin knocking-down causes cell cycle arrest and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells via p53 and p21Waf1/Cip1 up-regulation.

    Science.gov (United States)

    Rahmati, Marveh; Moosavi, Mohammad Amin; Zarghami, Nosratollah

    2014-12-01

    Nucleostemin (NS), a recently discovered nucleolar protein, is essential for maintaining self-renewal and proliferation of embryonic and adult stem cells as well as cancerous cells. The aim of this study was to determine biological function of NS in MOLT-4 cells as a human T-cell acute lymphocytic leukemia (T-ALL) model. Efficacy of a specific small interference RNA on NS depletion was studied by quantitative polymerase chain reaction and western blotting. The growth rate and viability were analyzed by trypan blue exclusion test. Fluorescent microscopy was used for detecting apoptosis. Cell cycle and apoptosis were mechanistically studied by flow cytometry and western blotting. Knockdown of NS inhibited proliferation, arrested the cell cycle, and induced apoptosis through p53 and p21(Waf1/Cip1) pathways in MOLT-4 cells. These findings demonstrate critical roles of NS in MOLT-4 cells and may implicate on its therapeutic potential in this human T-ALL model.

  14. Microcollinearity between autopolyploid sugarcane and diploid sorghum genomes

    Directory of Open Access Journals (Sweden)

    Rokhsar Daniel S

    2010-04-01

    Full Text Available Abstract Background Sugarcane (Saccharum spp. has become an increasingly important crop for its leading role in biofuel production. The high sugar content species S. officinarum is an octoploid without known diploid or tetraploid progenitors. Commercial sugarcane cultivars are hybrids between S. officinarum and wild species S. spontaneum with ploidy at ~12×. The complex autopolyploid sugarcane genome has not been characterized at the DNA sequence level. Results The microsynteny between sugarcane and sorghum was assessed by comparing 454 pyrosequences of 20 sugarcane bacterial artificial chromosomes (BACs with sorghum sequences. These 20 BACs were selected by hybridization of 1961 single copy sorghum overgo probes to the sugarcane BAC library with one sugarcane BAC corresponding to each of the 20 sorghum chromosome arms. The genic regions of the sugarcane BACs shared an average of 95.2% sequence identity with sorghum, and the sorghum genome was used as a template to order sequence contigs covering 78.2% of the 20 BAC sequences. About 53.1% of the sugarcane BAC sequences are aligned with sorghum sequence. The unaligned regions contain non-coding and repetitive sequences. Within the aligned sequences, 209 genes were annotated in sugarcane and 202 in sorghum. Seventeen genes appeared to be sugarcane-specific and all validated by sugarcane ESTs, while 12 appeared sorghum-specific but only one validated by sorghum ESTs. Twelve of the 17 sugarcane-specific genes have no match in the non-redundant protein database in GenBank, perhaps encoding proteins for sugarcane-specific processes. The sorghum orthologous regions appeared to have expanded relative to sugarcane, mostly by the increase of retrotransposons. Conclusions The sugarcane and sorghum genomes are mostly collinear in the genic regions, and the sorghum genome can be used as a template for assembling much of the genic DNA of the autopolyploid sugarcane genome. The comparable gene density between

  15. Fasciola hepatica from naturally infected sheep and cattle in Great Britain are diploid.

    Science.gov (United States)

    Beesley, N J; Cwiklinski, K; Williams, D J L; Hodgkinson, J

    2015-08-01

    Diploid (2n = 2x = 20) and triploid (2n = 3x = 30) Fasciola hepatica have been reported in the UK, and in Asia diploid, triploid and mixoploid (2x/3x) Fasciola spp. exist but there is little information to indicate how common triploidy is, particularly in UK fluke. Here the ploidy of 565 adult F. hepatica from 66 naturally infected British sheep and 150 adult F. hepatica from 35 naturally infected British cattle was determined. All 715 of these parasites were diploid, based on observation of 10 bivalent chromosomes and sperm (n = 335) or, since triploids are aspermic, sperm alone (n = 380). This constitutes the first extensive analysis of the ploidy of F. hepatica field isolates from Great Britain and shows that most F. hepatica isolated from cattle and sheep are diploid and have the capacity to sexually reproduce. These data suggest that triploidy, and by extension parthenogenesis, is rare or non-existent in wild British F. hepatica populations. Given that F. hepatica is the only species of Fasciola present in Britain our results indicate that the parasite is predominantly diploid in areas where F. hepatica exists in isolation and suggests that triploidy may only originate in natural populations where co-infection of F. hepatica and its sister species Fasciola gigantica commonly occurs.

  16. Comparative analysis of inbred and hybrid maize at the diploid and tetraploid levels.

    Science.gov (United States)

    Riddle, Nicole C; Birchler, James A

    2008-02-01

    Heterosis often occurs in offspring derived from a cross between inbred or divergent parents and can be observed as the superior performance of these hybrids for a wide variety of characters. Heterosis was compared in maize lines at two ploidy levels, diploid and tetraploid, to gain a better understanding of the interaction of heterosis and ploidy level. Employing genetically identical diploid and tetraploid maize derived from four different inbred lines, we investigated heterosis for 11 morphological traits, including several plant height measures, as well as flowering time for both silks and anthers. We find that the heterotic response of a certain hybrid differs between diploid and tetraploid lines, and that the response at one ploidy cannot serve as a predictor for the other. Also, progressive heterosis was found for several of the characters in the tetraploid double-cross hybrid, which can have four different alleles at one locus, compared to the double-cross diploid hybrids, which can only possess two alleles per locus. Overall, the results indicate that the heterotic response of tetraploid maize lines differs significantly from that of the diploid.

  17. Comparison of leaf proteomes of cassava (Manihot esculenta Crantz cultivar NZ199 diploid and autotetraploid genotypes.

    Directory of Open Access Journals (Sweden)

    Feifei An

    Full Text Available Cassava polyploid breeding has drastically improved our knowledge on increasing root yield and its significant tolerance to stresses. In polyploid cassava plants, increases in DNA content highly affect cell volumes and anatomical structures. However, the mechanism of this effect is poorly understood. The purpose of the present study was to compare and validate the changes between cassava cultivar NZ199 diploid and autotetraploid at proteomic levels. The results showed that leaf proteome of cassava cultivar NZ199 diploid was clearly differentiated from its autotetraploid genotype using 2-DE combined MS technique. Sixty-five differential protein spots were seen in 2-DE image of autotetraploid genotype in comparison with that of diploid. Fifty-two proteins were identified by MALDI-TOF-MS/MS, of which 47 were up-regulated and 5 were down-regulated in autotetraploid genotype compared with diploid genotype. The classified functions of 32 up-regulated proteins were associated with photosynthesis, defense system, hydrocyanic acid (HCN metabolism, protein biosynthesis, chaperones, amino acid metabolism and signal transduction. The remarkable variation in photosynthetic activity, HCN content and resistance to salt stress between diploid and autotetraploid genotypes is closely linked with expression levels of proteomic profiles. The analysis of protein interaction networks indicated there are direct interactions between the 15 up-regulation proteins involved in the pathways described above. This work provides an insight into understanding the protein regulation mechanism of cassava polyploid genotype, and gives a clue to improve cassava polyploidy breeding in increasing photosynthesis and resistance efficiencies.

  18. Comparison of leaf proteomes of cassava (Manihot esculenta Crantz) cultivar NZ199 diploid and autotetraploid genotypes.

    Science.gov (United States)

    An, Feifei; Fan, Jie; Li, Jun; Li, Qing X; Li, Kaimian; Zhu, Wenli; Wen, Feng; Carvalho, Luiz J C B; Chen, Songbi

    2014-01-01

    Cassava polyploid breeding has drastically improved our knowledge on increasing root yield and its significant tolerance to stresses. In polyploid cassava plants, increases in DNA content highly affect cell volumes and anatomical structures. However, the mechanism of this effect is poorly understood. The purpose of the present study was to compare and validate the changes between cassava cultivar NZ199 diploid and autotetraploid at proteomic levels. The results showed that leaf proteome of cassava cultivar NZ199 diploid was clearly differentiated from its autotetraploid genotype using 2-DE combined MS technique. Sixty-five differential protein spots were seen in 2-DE image of autotetraploid genotype in comparison with that of diploid. Fifty-two proteins were identified by MALDI-TOF-MS/MS, of which 47 were up-regulated and 5 were down-regulated in autotetraploid genotype compared with diploid genotype. The classified functions of 32 up-regulated proteins were associated with photosynthesis, defense system, hydrocyanic acid (HCN) metabolism, protein biosynthesis, chaperones, amino acid metabolism and signal transduction. The remarkable variation in photosynthetic activity, HCN content and resistance to salt stress between diploid and autotetraploid genotypes is closely linked with expression levels of proteomic profiles. The analysis of protein interaction networks indicated there are direct interactions between the 15 up-regulation proteins involved in the pathways described above. This work provides an insight into understanding the protein regulation mechanism of cassava polyploid genotype, and gives a clue to improve cassava polyploidy breeding in increasing photosynthesis and resistance efficiencies.

  19. Optimizing asparaginase therapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Rizzari, Carmelo; Conter, Valentino; Starý, Jan; Colombini, Antonella; Moericke, Anja; Schrappe, Martin

    2013-03-01

    Asparaginases are important agents used in the treatment of children with acute lymphoblastic leukemia (ALL). Three types of asparaginase are currently available: two are derived from Escherichia coli [native asparaginase and pegylated asparaginase (PEG-asparaginase)] and one from Erwinia chrysanthemi (crisantaspase). All three products share the same mechanism of action but have different pharmacokinetic properties, which do not make them easily interchangeable. Among the known toxicities and side-effects, allergic reactions and silent inactivation represent the most important limitations to the prolonged use of any asparaginase product, with associated reduced therapeutic effects and poorer outcomes. Routine real time monitoring can help to identify patients with silent inactivation and facilitate a switch to a different product to ensure continued depletion of asparagine, completion of the treatment schedule and maintenance of outcomes. However, the most appropriate second-line treatment is still a matter of debate. PEG-asparaginase has lower immunogenicity and a longer half-life than native Escherichia coli (E. coli) asparaginase, which makes it useful for both first-line and second-line use with a reduced number of doses. However, PEG-asparaginase displays cross-reactivity with native E. coli asparaginase that may harm its therapeutic effects. Crisantaspase does not display cross-reactivity to either of the E. coli-derived products, which has made crisantaspase the second-line treatment option in a number of recent protocols. As crisantaspase has a much shorter biological half-life than the E. coli-derived products, the appropriate dosage and administration schedule are of paramount importance in delivering treatment with this product. In the ongoing trial AIEOP-BFM ALL 2009 (Associazione Italiana Ematologia Oncologia Pediatrica - Berlin-Franklin-Munster), in which PEG-asparaginase is used first-line, one dose of PEG-asparaginase is substituted by seven doses

  20. 重组人白介素11对儿童急性淋巴细胞白血病化疗后血小板减少的疗效观察%Effects of recombinant human interleukin 11 treatment on thrombocytopenia induced by chemotherapy in children with acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    梁卉; 刘华林; 宋亮

    2011-01-01

    Objective To investigate the effects of recombinant human interleukin-11 (rhIL-11 ) treatment on thrombocytopenia in childhood acute lymphoblastic leukemia (ALL) after chemotherapy. Methods Total of 36 patients of childhood ALL suffering thrombocytopenia were randomly divided into treatment group and control group. Twenty-four hours after chemotherapy, only patients of the treatment group were given daily subcutaneous injection of rhIL-11 for 5 days. Changes of the platelet count were observed, the amount of platelet transfusion and adverse reactions were recorded. Results Compared with the control group, recovery time of platelet count was shorter, platelet transfusion was less in the treatment group, and the differences were statistically significant, while adverse reaction was mild.Conclusions Application of rhIL-11 can improve platelet count obviously after chemotherapy of ALL children, reduce platelet transfusion, and it is clinically safe and affordable.%目的 观察重组人白介素11(rhIL-11)对急性淋巴细胞白血病(ALL)患儿化疗后血小板减少的疗效和安全性.方法 选取36例ALL化疗后血小板减少患儿,随机分为治疗组和对照组,治疗组患儿在化疗结束后24 h每日皮下注射rhIL-11,应用5 d;对照组不用rhIL-11.观察两组患儿血小板数值变化,记录血小板输注量及治疗组不良反应.结果 治疗组较对照组血小板恢复时间短,输注血小板少,差异有统计学意义.治疗组rhIL-11不良反应轻微.结论 rhIL-11能明显提高儿童ALL化疗后血小板数量,减少血小板输注,临床应用安全,综合临床费用降低.

  1. Increase in mitotic recombination in diploid cells of Aspergillus nidulans in response to ethidium bromide

    Directory of Open Access Journals (Sweden)

    Tânia C.A. Becker

    2003-01-01

    Full Text Available Ethidium bromide (EB is an intercalating inhibitor of topoisomerase II and its activities are related to chemotherapeutic drugs used in anti-cancer treatments. EB promotes several genotoxic effects in exposed cells by stabilising the DNA-enzyme complex. The recombinagenic potential of EB was evaluated in our in vivo study by the loss of heterozygosity of nutritional markers in diploid Aspergillus nidulans cells through Homozygotization Index (HI. A DNA repair mutation, uvsZ and a chromosome duplication DP (II-I were introduced in the genome of tested cells to obtain a sensitive system for the recombinagenesis detection. EB-treated diploid cells had HI values significantly greater than the control at both concentrations (4.0 x 10-3 and 5.0 x 10-3 mM. Results indicate that the intercalating agent is potentially capable of inducing mitotic crossing-over in diploid A. nidulans cells.

  2. The physiological response of diploid and triploid brook trout to exhaustive exercise.

    Science.gov (United States)

    Hyndman, C A; Kieffer, J D; Benfey, T J

    2003-01-01

    Using triploidy as an experimental model, we examined whether cell size limits the post-exercise recovery process in fish. Because triploids generally possess larger cells, which could affect many physiological and biochemical processes, we hypothesized that triploids would take longer to recover from exhaustive exercise compared to diploids. To test this, we measured plasma lactate, glucose and osmolality, and white muscle energy stores (glycogen, phosphocreatine and ATP) and lactate before and immediately following exhaustive exercise and during recovery at 2 and 4 h post-exercise. In addition, oxygen consumption and ammonia excretion rates were determined before and after exhaustive exercise. Overall, diploid and triploid brook trout showed similar metabolic responses exercise, but plasma osmolality, white muscle lactate, white muscle ATP and post-exercise oxygen consumption rates recovered earlier in triploids compared to diploids. The results of this study suggest that the characteristic larger cell size of triploidy does not limit the physiological response to, or recovery from, exhaustive exercise.

  3. Development and characterization of microsatellite loci for the haploid-diploid red seaweed Gracilaria vermiculophylla.

    Science.gov (United States)

    Kollars, Nicole M; Krueger-Hadfield, Stacy A; Byers, James E; Greig, Thomas W; Strand, Allan E; Weinberger, Florian; Sotka, Erik E

    2015-01-01

    Microsatellite loci are popular molecular markers due to their resolution in distinguishing individual genotypes. However, they have rarely been used to explore the population dynamics in species with biphasic life cycles in which both haploid and diploid stages develop into independent, functional organisms. We developed microsatellite loci for the haploid-diploid red seaweed Gracilaria vermiculophylla, a widespread non-native species in coastal estuaries of the Northern hemisphere. Forty-two loci were screened for amplification and polymorphism. Nine of these loci were polymorphic across four populations of the extant range with two to eleven alleles observed. Mean observed and expected heterozygosities ranged from 0.265 to 0.527 and 0.317 to 0.387, respectively. Overall, these markers will aid in the study of the invasive history of this seaweed and further studies on the population dynamics of this important haploid-diploid primary producer.

  4. Development and characterization of microsatellite loci for the haploid–diploid red seaweed Gracilaria vermiculophylla

    Science.gov (United States)

    Byers, James E.; Greig, Thomas W.; Strand, Allan E.; Weinberger, Florian

    2015-01-01

    Microsatellite loci are popular molecular markers due to their resolution in distinguishing individual genotypes. However, they have rarely been used to explore the population dynamics in species with biphasic life cycles in which both haploid and diploid stages develop into independent, functional organisms. We developed microsatellite loci for the haploid–diploid red seaweed Gracilaria vermiculophylla, a widespread non-native species in coastal estuaries of the Northern hemisphere. Forty-two loci were screened for amplification and polymorphism. Nine of these loci were polymorphic across four populations of the extant range with two to eleven alleles observed. Mean observed and expected heterozygosities ranged from 0.265 to 0.527 and 0.317 to 0.387, respectively. Overall, these markers will aid in the study of the invasive history of this seaweed and further studies on the population dynamics of this important haploid–diploid primary producer. PMID:26339541

  5. Development and characterization of microsatellite loci for the haploid–diploid red seaweed Gracilaria vermiculophylla

    Directory of Open Access Journals (Sweden)

    Nicole M. Kollars

    2015-08-01

    Full Text Available Microsatellite loci are popular molecular markers due to their resolution in distinguishing individual genotypes. However, they have rarely been used to explore the population dynamics in species with biphasic life cycles in which both haploid and diploid stages develop into independent, functional organisms. We developed microsatellite loci for the haploid–diploid red seaweed Gracilaria vermiculophylla, a widespread non-native species in coastal estuaries of the Northern hemisphere. Forty-two loci were screened for amplification and polymorphism. Nine of these loci were polymorphic across four populations of the extant range with two to eleven alleles observed. Mean observed and expected heterozygosities ranged from 0.265 to 0.527 and 0.317 to 0.387, respectively. Overall, these markers will aid in the study of the invasive history of this seaweed and further studies on the population dynamics of this important haploid–diploid primary producer.

  6. Genetic selection and liquid medium conditions improve the yield of androgenetic plants from diploid potatoes.

    Science.gov (United States)

    Uhrig, H

    1985-12-01

    Solatium tuberosum L. diploid strains with superior androgenetic capacity have been selected for from androgenetic progenies of unselected diploid material. The paper also demonstrates that the use of a liquid medium for culturing potato anthers, instead of the conventional solid agar plates, improves the yield of androgenetic embryoids. The new method, associated with two successive cycles of selection for superior androgenetic response, allows the induction and regeneration of microspore derived plants on a large scale. The best genotype (clone 21 in this paper) regenerates androgenetic plants with a frequency around 30 per each anther plated. Over 80% of the regenerated plants are diploid. It is suggested that the androgenetic embryoids mainly originate from unreduced microspores by a mechanism which maintains a heterozygous or a partly heterozygous genetic situation.

  7. Massive Production of All-female Diploids and Triploids in the Crucian Carp

    Directory of Open Access Journals (Sweden)

    KaiKun Luo, Jun Xiao, ShaoJun Liu, Jing Wang, WeiGuo He, Jie Hu, QinBo Qin, Chun Zhang, Min Tao, Yun Liu

    2011-01-01

    Full Text Available In many species of aquaculture importance, all-female and sterile populations possess superior productivity due to faster growth and a relatively homogenous size of individuals. However, the production of all-female and sterile fish in a large scale for aquaculture is a challenge in practice, because treatments necessary for gynogenesis induction usually cause massive embryonic and larval mortality, and the number of induced gynogens is too small for their direct use in aquaculture. Here we report the massive production of all-female triploid crucian carp by combining artificial gynogenesis, sex reversal and diploid-tetraploid hybridization. Previously, we have obtained an allotetraploid carp population (4n = 200 by hybridization between red crucian carp (Carassius auratus red var; ♀ and common carp (Cyprinus carpio; ♂. We induced all-female diploid gynogens of the Japanese crucian carp (Carassius cuvieri; 2n = 100. We also generated male diploid gynogens of the same species treated gynogenetic fry with 17-α-methyltestosterone, leading to the production of sex-revered gynogenetic males. Finally, these males were used to cross with the female diploid Japanese crucian carp gynogens and the allotetraploid females, resulting in the production of fertile all-female diploid Japanese crucian carp (2n=100 and sterile all-female triploid hybrids (3n = 150, respectively. Therefore, diploid crucian carp gynogenetic females and sex-reversed male together with an allotetraploid line provide an opportunity to produce all-female triploid populations in a large scale to meet demands in aquaculture industry.

  8. Evolutionary origin and phylogeography of the diploid obligate parthenogen Artemia parthenogenetica (Branchiopoda: Anostraca.

    Directory of Open Access Journals (Sweden)

    Joaquín Muñoz

    Full Text Available BACKGROUND: Understanding the evolutionary origin and the phylogeographic patterns of asexual taxa can shed light on the origin and maintenance of sexual reproduction. We assessed the geographic origin, genetic diversity, and phylogeographic history of obligate parthenogen diploid Artemia parthenogenetica populations, a widespread halophilic crustacean. METHODOLOGY/PRINCIPAL FINDINGS: We analysed a partial sequence of the Cytochrome c Oxidase Subunit I mitochondrial gene from an extensive set of localities (including Eurasia, Africa, and Australia, and examined their phylogeographic patterns and the phylogenetic relationships of diploid A. parthenogenetica and its closest sexual relatives. Populations displayed an extremely low level of mitochondrial genetic diversity, with one widespread haplotype shared by over 79% of individuals analysed. Phylogenetic and phylogeographic analyses indicated a multiple and recent evolutionary origin of diploid A. parthenogenetica, and strongly suggested that the geographic origin of parthenogenesis in Artemia was in Central Asia. Our results indicate that the maternal sexual ancestors of diploid A. parthenogenetica were an undescribed species from Kazakhstan and A. urmiana. CONCLUSIONS/SIGNIFICANCE: We found evidence for multiple origin of parthenogenesis in Central Asia. Our results indicated that, shortly after its origin, diploid A. parthenogenetica populations underwent a rapid range expansion from Central Asia towards the Mediterranean region, and probably to the rest of its current geographic distribution. This contrasts with the restricted geographic distribution, strong genetic structure, and regional endemism of sexual Artemia lineages and other passively dispersed sexual continental aquatic invertebrates. We hypothesize that diploid parthenogens might have reached their current distribution in historical times, with a range expansion possibly facilitated by an increased availability of suitable

  9. Patterns of DNA cytosine methylation between haploids and corresponding diploids in rice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hongyu; PENG Hai; LI Yun; XU Peizhou; WANG Xudong; WU Xianjun

    2006-01-01

    Eighteen pairs of diploid-haploid twinseedlings were identified and screened out from special rice SARⅡ-628 population. Five pairs of them were selected and randomly designated as A, B, C, D and E. Simple sequence repeats (SSR) analysis showed that there was no difference among 310 sites,which indicated that there was no base mutation on DNA primary structure. DNA methylation plays an important role in gene expression regulation during growth and development stages in eukaryotes. A modified AFLP technique (methylation-sensitive AFLP, MSAP) was employed to detect the DNA methylation patterns in the 5'-CCGG sites of the five pairs of twin-seedlings. Although no methylation mutation was detected among the five diploids,forty-three methylation mutation sites were found from the corresponding haploids. The MSAP ratios,which were the ratios of MSAP sites to the total amplified sites, in five haploids were 18.79%, 19.35%,18.49%, 18.45% and 18.75%, respectively. And corresponding full methylation levels (5'-CmCGG in double strands) of those haploids were 10.58%,11.3%, 10.11%, 10.09% and 10.34%, respectively.Both MSAP and full methylation levels in the five haploids were higher than that of their corresponding diploids, which suggested that hypermethylation occurred in some 5'-CCGG sites. Five types of MASP patterns among the five pairs of twin-seedlings were detected as follows: (1) no changes, methylation levels were the same in both haploids and diploids; (2)demethylation, diploid was methylated but no methylation in the same site in haploid; (3) hypermethylation, the methylation level in haploid was higher than those in diploid; (4) hypomethylation, methylation in haploid was lower than those in diploid; (5)undecided pattern, change trend of methylation levels in haploids was not decided. The bands of 18 sites were reclaimed, then sequenced and searched on website to determine the sites of those sequences on rice chromosomes. The result showed that the methylation

  10. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  11. Identification and cloning of a prethymic precursor T lymphocyte from a population of common acute lymphoblastic leukemia antigen (CALLA)-positive fetal bone marrow cells

    DEFF Research Database (Denmark)

    Hokland, P; Hokland, M; Daley, J

    1987-01-01

    We have cloned common acute lymphoblastic leukemia (CALLA)-positive cells from human fetal bone marrow containing less than 1 in 10,000 E-RFC in round-bottomed microtiter wells (one cell per well) using the autocloning unit of an EPICS-V cell sorter. Expansion of such cells (with IL-2 and heavily...... irradiated autologous thymocytes as feeder cells) resulted in growth in 6-14% of the wells (mean, 11%) with cells with mature T lymphocyte phenotype. Two-color fluorescence analysis of outgrowing cultures furthermore ascertained that these cells had differentiated through a phase of simultaneous expression...... of T4 and T8 antigens and at the same time expression of the thymocyte-associated T6 antigens. Thus, given the fact that 10-20% of T cell acute lymphoblastic leukemia (T-ALLs) are CALLA+, we have been able to identify a human prethymic T lymphocyte population that might be the normal counterpart...

  12. Biochemical evaluation of triploid progenies of diploid × tetraploid breeding populations of Camellia for genotypes rich in catechin and caffeine.

    Science.gov (United States)

    Das, Sourabh Kumar; Sabhapondit, Santanu; Ahmed, Giasuddin; Das, Sudripta

    2013-06-01

    To verify the quality of triploid varieties of Camellia tea species at the secondary metabolite level, we tested caffeine and catechin profiles of 97 F(1) segregating progenies in two breeding populations with a common tetraploid parent and diploid parents of two geographic and varietal origins. Catechin and caffeine levels of the triploid progenies were quantified and compared against their diploid parent. Some of the progenies showed better performance than their diploid parent. Most of the progenies of the diploid C. sinensis × tetraploid cross showed heterosis for caffeine and EGCG. Progenies of the C. assamica subsp. lasiocalyx × tetraploid cross showed heterosis for +C, EC, EGC, and TC. The genomic contributions of the diploid parent seem to be the main factor in the variation between the two populations. Our studies showed quantitative enhancement of some of the quality-related parameters in tea, providing a platform to refocus on this classical breeding approach for developing quality cultivars in tea.

  13. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    Directory of Open Access Journals (Sweden)

    Stephen E. Langabeer

    2016-01-01

    Full Text Available The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexisting JAK2 V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations of CALR in essential thrombocythemia appear to be associated with a distinct phenotype and a lower risk of thrombosis yet their impact on disease progression is less well defined. The as yet undescribed scenario of pro-B cell acute lymphoblastic leukemia arising in CALR mutated essential thrombocythemia is presented. Intensive treatment for the leukemia allowed for expansion of the original CALR mutated clone. Whether CALR mutations in myeloproliferative neoplasms predispose to the acquisition of additional malignancies, particularly lymphoproliferative disorders, is not yet known.

  14. New decision support tool for acute lymphoblastic leukemia classification

    Science.gov (United States)

    Madhukar, Monica; Agaian, Sos; Chronopoulos, Anthony T.

    2012-03-01

    In this paper, we build up a new decision support tool to improve treatment intensity choice in childhood ALL. The developed system includes different methods to accurately measure furthermore cell properties in microscope blood film images. The blood images are exposed to series of pre-processing steps which include color correlation, and contrast enhancement. By performing K-means clustering on the resultant images, the nuclei of the cells under consideration are obtained. Shape features and texture features are then extracted for classification. The system is further tested on the classification of spectra measured from the cell nuclei in blood samples in order to distinguish normal cells from those affected by Acute Lymphoblastic Leukemia. The results show that the proposed system robustly segments and classifies acute lymphoblastic leukemia based on complete microscopic blood images.

  15. Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); I.M. Appel (Inge); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2008-01-01

    textabstractCoagulation alterations may be involved in osteonecrosis in childhood acute lymphoblastic leukemia. Retrospectively, we evaluated the available coagulation parameters at diagnosis and during induction treatment of 161 acute lymphoblastic leukemia patients: 24 with symptomatic osteonecros

  16. The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, Marissa A. H.; Pluijm, Saskia M. F.; de Groot-Kruseman, Hester A.; te Winkel, Mariel L.; Fiocco, Martha; van den Akker, Erica L. T.; Hoogerbrugge, Peter; van den Berg, Henk; Leeuw, Jan A.; Bruin, Marrie C. A.; Bresters, Dorine; Veerman, Anjo J. P.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2015-01-01

    Body mass index and change in body mass index during treatment may influence treatment outcome of pediatric patients with acute lymphoblastic leukemia. However, previous studies in pediatric acute lymphoblastic leukemia reported contradictory results. We prospectively collected data on body composit

  17. Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Churchman, Michelle L; Low, Jonathan; Qu, Chunxu; Paietta, Elisabeth M; Kasper, Lawryn H; Chang, Yunchao; Payne-Turner, Debbie; Althoff, Mark J; Song, Guangchun; Chen, Shann-Ching; Ma, Jing; Rusch, Michael; McGoldrick, Dan; Edmonson, Michael; Gupta, Pankaj; Wang, Yong-Dong; Caufield, William; Freeman, Burgess; Li, Lie; Panetta, John C; Baker, Sharyn; Yang, Yung-Li; Roberts, Kathryn G; McCastlain, Kelly; Iacobucci, Ilaria; Peters, Jennifer L; Centonze, Victoria E; Notta, Faiyaz; Dobson, Stephanie M; Zandi, Sasan; Dick, John E; Janke, Laura; Peng, Junmin; Kodali, Kiran; Pagala, Vishwajeeth; Min, Jaeki; Mayasundari, Anand; Williams, Richard T; Willman, Cheryl L; Rowe, Jacob; Luger, Selina; Dickins, Ross A; Guy, R Kiplin; Chen, Taosheng; Mullighan, Charles G

    2015-09-14

    Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.

  18. Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model

    Science.gov (United States)

    The efficacy of orally and parenterally administered curcumin was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) acute lymphoblastic leukemia line SEM. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed...

  19. Acute lymphoblastic leukemia presenting with a uterine cervical mass

    Directory of Open Access Journals (Sweden)

    N Geetha

    2015-01-01

    Full Text Available Involvement of female genital tract with acute lymphoblastic leukemia (ALL is extremely rare, and it is even rarer for a patient to have symptomatic presentation. We report the case of a middle-aged lady with ALL, who presented with severe abnormal uterine bleeding and a uterine cervical mass. Biopsy of the cervical mass showed infiltration by leukemic blasts. She received chemotherapy with Berlin-Frankfurt-Munster protocol and is alive in remission after 10 years.

  20. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Nielsen, Stine N; Frandsen, Thomas L;

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug...... intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments, extensive host genome profiling to understand diversity in treatment efficacy and toxicity, and alternative thiopurine dosing regimens...

  1. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    OpenAIRE

    Soosay Raj TA; Smith AM; Moore AS

    2013-01-01

    Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a...

  2. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Maria de Fatima; Braga, Flavio Tulio [Federal University of Sao Paulo, Department of Diagnostic Imaging, Paulista School of Medicine, Sao Paulo (Brazil); Rocha, Antonio Jose da [Santa Casa de Misericordia de Sao Paulo, Servico de Diagnostico por Imagem, Sao Paulo (Brazil); Lederman, Henrique Manoel [Federal University of Sao Paulo, Division of Diagnostic Imaging in Pediatrics, Department of Diagnostic Imaging, Sao Paulo (Brazil)

    2005-08-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  3. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Efficient construction of homozygous diploid strains identifies genes required for the hyper-filamentous phenotype in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Kentaro Furukawa

    Full Text Available Yeast cells undergo diploid-specific developments such as spore formation via meiosis and pseudohyphal development under certain nutrient-limited conditions. Studies on these aspects require homozygous diploid mutants, which are generally constructed by crossing strains of opposite mating-type with the same genetic mutation. So far, there has been no direct way to generate and select diploids from haploid cells. Here, we developed a method for efficient construction of homozygous diploids using a PGAL1-HO gene (galactose-inducible mating-type switch and a PSTE18-URA3 gene (counter selection marker for diploids. Diploids are generated by transient induction of the HO endonuclease, which is followed by mating of part of the haploid population. Since the STE18 promoter is repressed in diploids, diploids carrying PSTE18-URA3 can be selected on 5-fluoroorotic acid (5-FOA plates where the uracil prototrophic haploids cannot grow. To demonstrate that this method is useful for genetic studies, we screened suppressor mutations of the complex colony morphology, strong agar invasion and/or hyper-filamentous growth caused by lack of the Hog1 MAPK in the diploid Σ1278b strain background. Following this approach, we identified 49 suppressor mutations. Those include well-known positive regulator genes for filamentous growth signaling pathways, genes involved in mitochondrial function, DNA damage checkpoint, chromatin remodeling, and cell cycle, and also previously uncharacterized genes. Our results indicate that combinatorial use of the PGAL1-HO and PSTE18-URA3 genes is suitable to efficiently construct and select diploids and that this approach is useful for genetic studies especially when combined with large-scale screening.

  5. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Mina Islambulchilar

    2015-03-01

    Full Text Available Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally. Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years. The results indicated that the levels of white blood cells are significantly (P<0.05 increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05 lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes.

  6. Evaluating the relationship between diploid and tetraploid Vaccinium oxycoccos (Ericaceae) in eastern Canada

    Science.gov (United States)

    Vaccinium oxycoccos s. l. is a complex of diploid and polyploid plants. The evolutionary relationship between the cytotypes is uncertain, with conflicting treatments in recent taxonomic studies. To clarify this situation, we investigated the relationships among ploidy, morphology and genetic diversi...

  7. The use of SNP markers for linkage mapping in diploid and tetraploid peanuts.

    Science.gov (United States)

    Bertioli, David J; Ozias-Akins, Peggy; Chu, Ye; Dantas, Karinne M; Santos, Silvio P; Gouvea, Ediene; Guimarães, Patricia M; Leal-Bertioli, Soraya C M; Knapp, Steven J; Moretzsohn, Marcio C

    2014-01-10

    Single nucleotide polymorphic markers (SNPs) are attractive for use in genetic mapping and marker-assisted breeding because they can be scored in parallel assays at favorable costs. However, scoring SNP markers in polyploid plants like the peanut is problematic because of interfering signal generated from the DNA bases that are homeologous to those being assayed. The present study used a previously constructed 1536 GoldenGate SNP assay developed using SNPs identified between two A. duranensis accessions. In this study, the performance of this assay was tested on two RIL mapping populations, one diploid (A. duranensis × A. stenosperma) and one tetraploid [A. hypogaea cv. Runner IAC 886 × synthetic tetraploid (A. ipaënsis × A. duranensis)(4×)]. The scoring was performed using the software GenomeStudio version 2011.1. For the diploid, polymorphic markers provided excellent genotyping scores with default software parameters. In the tetraploid, as expected, most of the polymorphic markers provided signal intensity plots that were distorted compared to diploid patterns and that were incorrectly scored using default parameters. However, these scorings were easily corrected using the GenomeStudio software. The degree of distortion was highly variable. Of the polymorphic markers, approximately 10% showed no distortion at all behaving as expected for single-dose markers, and another 30% showed low distortion and could be considered high-quality. The genotyped markers were incorporated into diploid and tetraploid genetic maps of Arachis and, in the latter case, were located almost entirely on A genome linkage groups.

  8. Karyotype Analysis in Wild Diploid, Tetraploid, and Hexaploid Strawberries, Fragaria (Rosaceae)

    Science.gov (United States)

    The Strawberry, genus Fragaria (Rosaceae) has a basic chromosome count of x = 7, and is comprised of 20 wild species having an euploid series from diploid (2n = 2x = 14) through decaploid (2n = 10x = 70). Few karyotypes of species in this genus have been reported. The objective of this research was ...

  9. FveGD: an online resource for diploid strawberry (fragaria vesca) genomics data

    Science.gov (United States)

    Fragaria vesca, a diploid strawberry species commonly known as the alpine or woodland strawberry, is a versatile experimental plant system that is an emerging model for the Rosaceae family. An ancestral F. vesca genome contributed to the genome of the octoploid dessert strawberry (F. xananassa) and...

  10. Diverse functions of KNOX transcription factors in the diploid body plan of plants

    Science.gov (United States)

    KNOX genes were initially found as shoot meristem regulators in angiosperms. Recent studies in diverse plant lineages however, have revealed the divergence of KNOX gene function during the evolution of diploid body plans. Using genomic approaches, class I KNOX transcription factors have been shown t...

  11. Genetic diversity of diploid Japanese strawberry species based on microsatellite markers

    Science.gov (United States)

    The United States Department of Agriculture (USDA) - Agricultural Research Service (ARS) - National Clonal Germplasm Repository (NCGR) in Corvallis, Oregon, is a genebank that preserves strawberry genetic resources. In 2004, representatives of two Japanese diploid species, F. iinumae Makino and F. n...

  12. The simulation of meiosis in diploid and tetraploid organisms using various genetic models

    NARCIS (Netherlands)

    Voorrips, R.E.; Maliepaard, C.A.

    2012-01-01

    Background: While the genetics of diploid inheritance are well studied and software for linkage mapping, haplotyping and QTL analysis are available, for tetraploids the available tools are limited. In order to develop such tools it would be helpful if simulated populations based on a variety of

  13. Diploid Musa acuminata genetic diversity assayed with sequence-tagged microsatellite sites.

    Science.gov (United States)

    Grapin, A; Noyer, J L; Carreel, F; Dambier, D; Baurens, F C; Lanaud, C; Lagoda, P J

    1998-06-01

    The sequence-tagged microsatellite site (STMS) discrimination potential was explored using nine microsatellite primer pairs. STMS polymorphism was assayed by nonradioactive urea-polyacrylamide gel electrophoresis. Genetic relationships were examined among 59 genotypes of wild or cultivated accessions of diploid Musa acuminata. The organization of the subspecies was confirmed and some clone relationships were clarified.

  14. Wolbachia endosymbionts in haplodiploid and diploid scolytine beetles (Coleoptera: Curculionidae: Scolytinae).

    Science.gov (United States)

    Kawasaki, Yuuki; Schuler, Hannes; Stauffer, Christian; Lakatos, Ferenc; Kajimura, Hisashi

    2016-05-19

    Haplodiploidy is a sex determination system in which fertilized diploid eggs develop into females and unfertilized haploid eggs develop into males. The evolutionary explanations for this phenomenon include the possibility that haplodiploidy can be reinforced by infection with endosymbiotic bacteria, such as Wolbachia. The subfamily Scolytinae contains species with haplodiploid and diploid sex determination systems. Thus, we studied the association with Wolbachia in 12 diploid and 11 haplodiploid scolytine beetles by analyzing wsp and multilocus sequence typing (MLST) of five loci in this endosymbiont. Wolbachia genotypes were compared with mitochondrial (COI) and nuclear (EF) genotypes in the scolytines. Eight of the 23 scolytine species were infected with Wolbachia, with haplodiploids at significantly higher rates than diploid species. Cloning and sequencing detected multiple infections with up to six Wolbachia strains in individual species. Phylogenetic analyses of wsp and five MLST genes revealed different Wolbachia strains in scolytines. Comparisons between the beetle and Wolbachia phylogenies revealed that closely related beetles were infected with genetically different Wolbachia strains. These results suggest the horizontal transmission of multiple Wolbachia strains between scolytines. We discuss these results in terms of the evolution of different sex determination systems in scolytine beetles. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  15. Aneuploid progenies of triploid hybrids between diploid and tetraploid loach Misgurnus anguillicaudatus in China.

    Science.gov (United States)

    Li, Ya-Juan; Gao, Yang-Chun; Zhou, He; Ma, Hai-Yan; Lin, Zhong-Qiao; Ma, Tian-Yu; Sui, Yi; Arai, Katsutoshi

    2016-10-01

    Triploid Chinese loach, Misgurnus anguillicaudatus, hybrids between tetraploids from Hubei Province and diploids from Liaoning Province were mated with either diploid wild-type or triploid hybrids to analyze viability and ploidy of the resultant progenies. Both triploid males and females generated fertile gametes, but progenies from the crosses using gametes of triploid hybrids did not survive beyond the larval stages. In crosses between wild-type diploid females and triploid hybrid males, embryos ranging from 2.2n to 2.6n were predominant with a mode of either 2.4n (chromosome numbers 59, 60, 61) or 2.5n (chromosome numbers 62, 63). Those from the crosses between triploid hybrid females and diploid males gave a modal ploidy level at approximately 2.5n in one case, but a shift to a higher ploidy level was observed in other embryos. In the progenies between triploid hybrid females and males, the ploidy level at approximately 3.0n (chromosome numbers 74, 75, 76) was most frequent. The cytogenetic results of the progenies suggest the production of aneuploid gametes with a modal ploidy level at approximately 1.5n in triploid hybrids. However, a shift to higher chromosome numbers in gametes was observed in certain cases, suggesting the involvement of mortality selection of gametes and/or zygotes with lower chromosome numbers.

  16. Mosaic haploid-diploid embryos and polyspermy in the tellinid bivalve Macoma balthica

    NARCIS (Netherlands)

    Luttikhuizen, PC; Pijnacker, LP

    2002-01-01

    We investigated meiosis, fertilization, and early development in eggs of the tellinid bivalve Macoma balthica (L.), which has external fertilization. Meiosis is standard but polyspermy is found to be very common. In all eight crosses examined, mosaic embryos consisting of a mixture of diploid (2n =

  17. A diploid inbred line strategy to accelerate genetic gain in potato

    Science.gov (United States)

    Breeding potato at the tetraploid level is inefficient and slow. Potato breeding has not kept pace with advances in breeding strategies and genomics tools. This project initiates our plan to convert potato into a diploid crop capable of self-pollination. This will allow breeders to realize the genet...

  18. The simulation of meiosis in diploid and tetraploid organisms using various genetic models

    NARCIS (Netherlands)

    Voorrips, R.E.; Maliepaard, C.A.

    2012-01-01

    Background: While the genetics of diploid inheritance are well studied and software for linkage mapping, haplotyping and QTL analysis are available, for tetraploids the available tools are limited. In order to develop such tools it would be helpful if simulated populations based on a variety of mode

  19. Tetraploid/Diploid Mosaicism in Cultured Genital Skin Fibroblasts : Is It Causally Related to Penoscrotal Hypospadias

    NARCIS (Netherlands)

    Giltay, Jacques C.|info:eu-repo/dai/nl/074049089; Klijn, Aart J.|info:eu-repo/dai/nl/304813486; de Jong, Tom P V M|info:eu-repo/dai/nl/111546443; Kats, Peter; van Breugel, Marjolein; Lens, Susan|info:eu-repo/dai/nl/175969973; Vromans, Martijn|info:eu-repo/dai/nl/314033734; Van Der Veken, Lars T.; Hochstenbach, Ron|info:eu-repo/dai/nl/117339067

    2016-01-01

    Tetraploid/diploid mosaicism is a rare chromosomal abnormality that is infrequently reported in patients with severe developmental delay, growth retardation, and short life span. Here, we present a 6-year-old patient with severe penoscrotal hypospadias and a coloboma of the left eye but with normal

  20. Induced Polyploidy in Diploid Ornamental Ginger (Hedychium muluense) Using Colchicine and Oryzalin

    Science.gov (United States)

    The ploidy level of H. muluense, a diploid (2n = 2x = 34) and dwarf ornamental ginger species, has been determined and is reported for the first time. Oryzalin and colchicine were successfully used to induce polyploidy in Hedychium muluense in vitro. Embryogenic cell lines were treated with oryzalin...

  1. Genetic Diversity and Relationships among Diploid and Tetraploid Cotton Using RAPD Markers

    Institute of Scientific and Technical Information of China (English)

    MOGHADDAM Mohammad Reza Ramazani; MAJIDI Eslam; MOFIDABADI Ali Jafari

    2008-01-01

    @@ Gossypium species (+49) represent a vast resource of genetic diversity for improvement of cultivated cotton.To determine intra- and inter-specific genetic diversity and relationships,we employed 30 RAPD random detainer primers on twenty eight cotton accessions from 2 diploid cultivated species (G.arboreum,G.herbaceum) and 2 tetraploid cultivated species (G.hirsuturn,G.barbadense).

  2. Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Reynolds, C; Roderick, J E; LaBelle, J L; Bird, G; Mathieu, R; Bodaar, K; Colon, D; Pyati, U; Stevenson, K E; Qi, J; Harris, M; Silverman, L B; Sallan, S E; Bradner, J E; Neuberg, D S; Look, A T; Walensky, L D; Kelliher, M A; Gutierrez, A

    2014-09-01

    Treatment resistance in T-cell acute lymphoblastic leukemia (T-ALL) is associated with phosphatase and tensin homolog (PTEN) deletions and resultant phosphatidylinositol 3'-kinase (PI3K)-AKT pathway activation, as well as MYC overexpression, and these pathways repress mitochondrial apoptosis in established T-lymphoblasts through poorly defined mechanisms. Normal T-cell progenitors are hypersensitive to mitochondrial apoptosis, a phenotype that is dependent on the expression of proapoptotic BIM. In a conditional zebrafish model, MYC downregulation induced BIM expression in T-lymphoblasts, an effect that was blunted by expression of constitutively active AKT. In human T-ALL cell lines and treatment-resistant patient samples, treatment with MYC or PI3K-AKT pathway inhibitors each induced BIM upregulation and apoptosis, indicating that BIM is repressed downstream of MYC and PI3K-AKT in high-risk T-ALL. Restoring BIM function in human T-ALL cells using a stapled peptide mimetic of the BIM BH3 domain had therapeutic activity, indicating that BIM repression is required for T-ALL viability. In the zebrafish model, where MYC downregulation induces T-ALL regression via mitochondrial apoptosis, T-ALL persisted despite MYC downregulation in 10% of bim wild-type zebrafish, 18% of bim heterozygotes and in 33% of bim homozygous mutants (P=0.017). We conclude that downregulation of BIM represents a key survival signal downstream of oncogenic MYC and PI3K-AKT signaling in treatment-resistant T-ALL.

  3. 人急性B淋巴细胞白血病-NOD/SCID/IL2rγnull新生小鼠异种移植模型的建立%Establishment of Human Acute B-Lymphoblastic Leukemia NOD/SCID/ IL2 Receptor γChainnull neonatal Mouse Xenotransplant Model

    Institute of Scientific and Technical Information of China (English)

    孔圆; 刘艳荣; 刘开彦; 黄晓军; Fumihiko Ishikawa; Mine Harada

    2012-01-01

    In order to study human acute B-lymphoblastic leukemia (B-ALL) in vivo, a novel xenotransplant model was established by using neonaial NOD/SCID/IL2 receptor γ chainmall mouse. The CD34+CD19+ bone marrow ( BM) cells were sorted from the CD3- CD4- CD8- fraction of B-ALL patients by fluorescence-activated cell sorting( FACS), and injected into 100 cGy irradiated neonatal NOD/SCID/IL2γmall mice through facial vein. The engraftment and proliferation of human B-ALL cells were monitored by the presence of human CD45+ CD19+ cells in peripheral blood (PB). Human hematopoietic chimerism in PB, BM and spleen of the recipients was examined by multi parameter flow cytometry. Morphological analyses of FACS-sorted murine marrow cells were performed by using May-Grunwald-Giemsa staining. Furthermore, leukemia cell infiltration in the organs was evaluated by hematoxylin-eosin staining. The results indicated that the sorted CD34+ CD19+ cells were able to initiate human B-ALL in vivo. The percentages of humanCms+CD19+ cells in PB, BM and spleen of the recipient mice were (83. 36 ± 10.05)% , (93.88 ±5.05)% and (88.31 ±5.01)% , respectively. Furthermore, the phenotype and morphology of the engrafted human cells were resemble to the original B-ALL cells from the patients. Similar to the clinical features, transplanted leukemic cells infiltrated into the organs, such as liver, lung, kidney and brain in the recipients. It is concluded that neonatal NOD/ SCID/IL2rγnull mice can support efficient engraftment of the sorted CD34+ CD19+ cells from human B-ALL for a long-term period. Human-mouse xenotransplant model using neonatal NOD/SCID/IL2rγnull mouse may provide an important system to study the biology of human B-ALL in vivo.%本研究旨在应用NOD/SCID/Ⅱ2rγnull新生小鼠建立人急性B淋巴细胞白血病(B-ALL)的异种移植模型.NOD/SCID/Ⅱ2rγnull新生期(出生48h之内)小鼠经亚致死剂量(100 cGy) 137Cs全身照射后,由面静脉输注FACSAria流式细胞

  4. Temporal and Developmental-Stage Variation in the Occurrence of Mitotic Errors in Tripronuclear Human Preimplantation Embryos

    NARCIS (Netherlands)

    Mantikou, Eleni; van Echten-Arends, Jannie; Sikkema-Raddatz, Birgit; van der Veen, Fulco; Repping, Sjoerd; Mastenbroek, Sebastiaan

    2013-01-01

    Mitotic errors during early development of human preimplantation embryos are common, rendering a large proportion of embryos chromosomally mosaic. It is also known that the percentage of diploid cells in human diploid-aneuploid mosaic embryos is higher at the blastocyst than at the cleavage stage. I

  5. Acute Lymphoblastic Leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available estigation E.1.1Medical condition(s) being investigated Acute Lymphoblastic Leukemia E.1.1.1Medical conditio...E.1.2Version 18.0 E.1.2Level LLT E.1.2Classification code 10000845 E.1.2Term Acute lymphoblastic leukemia E.

  6. Transformation of Myelodysplastic Syndrome to Acute Lymphoblastic Leukemia in a Child

    OpenAIRE

    2010-01-01

    Childhood myelodysplastic syndrome (MDS) is an uncommon condition. Unlike adult MDS, pediatric patients have a more progressive course and rapidly transform to acute myeloid leukemia. Evolution to acute lymphoblastic leukemia is extremely rare. We report a 5 year old female child who presented with refractory anemia with excess blasts and transformed into acute lymphoblastic leukemia 4 months after initial diagnosis.

  7. Proteomic profile of pre - B2 lymphoblasts from children with acute lymphoblastic leukemia (ALL) in relation with the translocation (12; 21)

    National Research Council Canada - National Science Library

    Costa, Odile; Schneider, Pascale; Coquet, Laurent; Chan, Philippe; Penther, Dominique; Legrand, Elisabeth; Jouenne, Thierry; Vasse, Marc; Vannier, Jean-Pierre

    2014-01-01

    ...), indicator of good prognosis, usually.Protein expression in pre-B2 lymphoblastic cells, collected from residual bone marrow cells after diagnostic procedures, was analyzed using two dimensional gel electrophoresis protocol...

  8. Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

    Science.gov (United States)

    Al-Absi, Boshra; Noor, Suzita M; Saif-Ali, Riyadh; Salem, Sameer D; Ahmed, Radwan H; Razif, Muhammad Fm; Muniandy, Sekaran

    2017-04-01

    Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was

  9. SCENARIO OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN GWALIOR REGION

    Directory of Open Access Journals (Sweden)

    Mangal

    2016-04-01

    Full Text Available BACKGROUND Leukaemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukaemia (ALL constitutes about 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early diagnosis of this haematological malignancy can be helpful for prognosis of disease. AIMS AND OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS AND METHODS The present study (2014 was performed in the Department of Pathology of Gajra Raja Medical College, Gwalior, over a period of one year from October 2013 to September 2014. The blood samples were received from patients attending various Departments of Jayarogya Groups of Hospitals, a tertiary care hospital. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukaemia, 25 (67.57% were male and 12 (32.43% were female, (male:female ratio: 2.1:1; 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27%, while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal White Blood Cell (WBC count at presentation with about 80% were presented with Leukocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukaemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  10. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Shiek Aejaz Aziz

    2015-01-01

    Full Text Available Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 patients of all age groups were enrolled for the study, of which flow cytometry was done in 144 patients. Statistical Analysis Used: Analysis was done using the variables on SPSS (statistical package for social sciences software on computer. Survival curves were estimated by method of Kaplan-Meir. Results: Majority of the patients were of B-cell (68.1% and 30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa positivity. Complete remission (CR was achieved in 59.1%, 16.4% relapsed, and 20.1% patients died. Conclusions: Phenotyping has become an important and integral part of diagnosis, classification, management and prognosticating in ALL. B-cell has been found to have a better survival over T-cell lymphoblastic leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell lineage, myeloid coexpression has no significant effect on the outcome. BFM (Berlin-Frankfurt-Münster based protocols though showed a higher CR and survival vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk category and lesser in numbers cannot be compared statistically with a fair degree of confidence.

  11. Comparative cytogenetic analysis of Avena macrostachya and diploid C-genome Avena species.

    Science.gov (United States)

    Badaeva, Ekaterina D; Shelukhina, Olga Yu; Diederichsen, Axel; Loskutov, Igor G; Pukhalskiy, Vitaly A

    2010-02-01

    The chromosome set of Avena macrostachya Balansa ex Coss. et Durieu was analyzed using C-banding and fluorescence in situ hybridization with 5S and 18S-5.8S-26S rRNA gene probes, and the results were compared with the C-genome diploid Avena L. species. The location of major nucleolar organizer regions and 5S rDNA sites on different chromosomes confirmed the affiliation of A. macrostachya with the C-genome group. However, the symmetric karyotype, the absence of "diffuse heterochromatin" and the location of large C-band complexes in proximal chromosome regions pointed to an isolated position of A. macrostachya from other Avena species. Based on the distribution of rDNA loci on the C-genome chromosomes of diploid and polyploid Avena species, we propose a model of the chromosome alterations that occurred during the evolution of oat species.

  12. A rigorous model study of the adaptative dynamics of Mendelian diploids

    CERN Document Server

    Collet, Pierre; Metz, J A J

    2011-01-01

    Adaptive dynamics so far has been put on a rigorous footing only for clonal inheritance. We extend this to sexually reproducing diploids, although admittedly still under the restriction of an unstructured population with Lotka-Volterra-like dynamics and single locus genetics (as in Kimura's 1965 infinite allele model). We prove under the usual smoothness assumptions, starting from a stochastic birth and death process model, that, when advantageous mutations are rare and mutational steps are not too large, the population behaves on the mutational time scale (the 'long' time scale of the literature on the genetical foundations of ESS theory) as a jump process moving between homozygous states (the trait substitution sequence of the adaptive dynamics literature). Essential technical ingredients are a rigorous estimate for the probability of invasion in a dynamic diploid population, a rigorous, geometric singular perturbation theory based, invasion implies substitution theorem, and the use of the Skorohod $M_1$ to...

  13. Production of Early Diploid Males by European Colonies of the Invasive Hornet Vespa velutina nigrithorax.

    Science.gov (United States)

    Darrouzet, Eric; Gévar, Jérémy; Guignard, Quentin; Aron, Serge

    2015-01-01

    The invasive yellow-legged hornet Vespa velutina nigrithorax was accidentally introduced in Europe in the early 2000s. As is the case in colonies of other wasp and hornet species, V. velutina colonies are known to produce sexuals (males and new queens) at the end of the summer. We show that early-stage colonies in French populations frequently produce males well before the usual reproductive period. The vast majority of the males produced are diploid, which is consistent with the loss of genetic diversity previously reported in introduced populations in France. Since males do not participate in colony activities, the production of early diploid males at the expense of workers is expected to hamper colony growth and, ultimately, decrease the expansion of the species in its invasive range in Europe.

  14. Production of Early Diploid Males by European Colonies of the Invasive Hornet Vespa velutina nigrithorax.

    Directory of Open Access Journals (Sweden)

    Eric Darrouzet

    Full Text Available The invasive yellow-legged hornet Vespa velutina nigrithorax was accidentally introduced in Europe in the early 2000s. As is the case in colonies of other wasp and hornet species, V. velutina colonies are known to produce sexuals (males and new queens at the end of the summer. We show that early-stage colonies in French populations frequently produce males well before the usual reproductive period. The vast majority of the males produced are diploid, which is consistent with the loss of genetic diversity previously reported in introduced populations in France. Since males do not participate in colony activities, the production of early diploid males at the expense of workers is expected to hamper colony growth and, ultimately, decrease the expansion of the species in its invasive range in Europe.

  15. Coexistence and performance of diploid and polyploid Acacia senegal (L.) Willd

    DEFF Research Database (Denmark)

    Diallo, Adja Madjiguene

    ). Sibling relationship among and between trees from the different open pollinated progenies was tested by application of genetic markers to support the quantitative genetic analysis. The results suggested different mating systems in diploid and polyploids, and this complicated the quantitative genetic...... a consistent effect on growth rate of the trees, but not on the economically important gum yield in the investigated years. Still, estimates of genetic parameters showed that gum yield is a heritable trait (based on analysis of diploids). The results therefore suggest that breeding for high gum yield could...... be effective. These results represent a good start-up for a future program of conservation, reforestation and restoration of A. senegal in the Sahel region....

  16. Allelic diversity and molecular characterization of puroindoline genes in five diploid species of the Aegilops genus.

    Science.gov (United States)

    Cuesta, Susana; Guzmán, Carlos; Alvarez, Juan B

    2013-11-01

    Grain hardness is an important quality trait in wheat. This trait is related to the variation in, and the presence of, puroindolines (PINA and PINB). This variation can be increased by the allelic polymorphism present in the Aegilops species that are related to wheat. This study evaluated allelic Pina and Pinb gene variability in five diploid species of the Aegilops genus, along with the molecular characterization of the main allelic variants found in each species. This polymorphism resulted in 16 alleles for the Pina gene and 24 alleles for the Pinb gene, of which 10 and 17, respectively, were novel. Diverse mutations were detected in the deduced mature proteins of these alleles, which could influence the hardness characteristics of these proteins. This study shows that the diploid species of the Aegilops genus could be a good source of genetic variability for both Pina and Pinb genes, which could be used in breeding programmes to extend the range of different textures in wheat.

  17. CLINICOPATHOLOGICAL STUDY OF ACUTE LYMPHOBLASTIC LEUKEMIA - A MULTIPARAMETER STUDY

    Directory of Open Access Journals (Sweden)

    Jagannath

    2015-11-01

    Full Text Available BACKGROUND Acute Lymphoblastic Leukaemia (ALL, a malignancy of lymphoid lineage cells, has excellent prognosis in children. Leukemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukemia (ALL constitutes 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early detection of clinical symptoms positively affects timely diagnosis. AIMS & OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS & METHODS The present study (2014 was performed in the hematology section of Department of Pathology of Gajra Raja Medical College, Gwalior over a period of 12 months from 1st October 2013 to 30th September 2014. This was a prospective study. The blood samples were received from various departments of Jayarogya hospital especially from the Pediatric and Medicine departments. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukemia, 25(67.57% were male and 12(32.43%, were female, (male:female ratio: 2.1:1. 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27% while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients, and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal white blood cell (WBC count at presentation, 10.81% had leucopenia and 80% had leucocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  18. Oral health of children with acute lymphoblastic leukemia: A review

    Directory of Open Access Journals (Sweden)

    Kadalagere Lakshmana Girish Babu

    2016-01-01

    Full Text Available Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in India. Advances in the treatment regimens have greatly increased the chances of survival. Both the disease and its treatment change the oral environment. In some cases, oral manifestations are the presenting feature of the disease and it will be the dentist′s responsibility to identify the underlying disorder and guide the diagnosis of the patient. Hence, the aim of present article is to review the literature concerning the oral health of children with acute lymphoblastic leukemia (ALL.

  19. [Disseminated fusariosis in a patient with acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Hermansen, N.E.; Ralfkiaer, E.M.; Kjeldsen, L.

    2008-01-01

    Invasive mould infections are a major cause of infectious mortality in highly immunosuppressed patients. Incidence in this high risk group is 10-20% with a death rate in excess of 50%. Most invasive moulds are Aspergillus spp. We present a case of a 74-year-old woman with acute lymphoblastic...... leukaemia who developed a rare disseminated mould infection with Fusarium solani during induction chemotherapy. We present the case story and discuss the pathogenesis, clinical characteristics and treatment of invasive fusariosis Udgivelsesdato: 2008/9/8...

  20. Testis Scintigraphy in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Mine Şencan Eren

    2014-02-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a pediatric malignancy associated with remissions and relapses. Common relapsing sitesare meninges, testis and ovary. Testicular scintigraphy is a highly specific modality used mainly in the differential diagnosis of testicular torsion and epidydimitis/epidydimo-orchitis. There is only one interesting image on leukemic infiltration with scrotal scintigraphy in the literature. The aim of this case presentation is to report that although the scintigraphic appearance of testicular torsion was observed in a patient with the diagnosis of ALL, testicular ALL infiltration was revealed in pathologic examination.

  1. Primary T-cell lymphoblastic lymphoma in the middle ear.

    Science.gov (United States)

    Li, Bo; Liu, Shixi; Yang, Hui; Wang, Weiya

    2016-03-01

    T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma characterized by precursor T-cell malignancy and lymphadenopathy or mediastinal involvement. We present the case of an 11-year-old boy with a diagnosis of middle ear T-LBL, which manifested as a headache, hearing loss and peripheral facial paralysis. The child was given intensive chemotherapy and had a complete response. To our knowledge, this is the first case reported in the literature of T-LBL originating in the middle ear. This case aims to help clinicians to be vigilant about the possibility of primary lesions at atypical sites in some special diseases.

  2. Clonal origins of ETV6-RUNX1+ acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Alpar, D.; Wren, D.; Ermini, Luca;

    2015-01-01

    Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, prenatal genetic event with other driver aberrations occurring subclonally and probably postnatally. The fetal cell type that is transformed by ETV6-RUNX1 is not identified...... by such studies or by the analysis of early B-cell lineage phenotype of derived progeny. Ongoing, clonal immunoglobulin (IG) and cross-lineage T-cell receptor (TCR) gene rearrangements are features of B-cell precursor leukemia and commence at the pro-B-cell stage of normal B-cell lineage development. We reasoned...

  3. Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

    Energy Technology Data Exchange (ETDEWEB)

    Bayrak, Ilkay Koray; Yalin, Turkay; Ozmen, Zafer; Aksoz, Tolga; Doughanji, Roula [Ondokuz Mayis University, Samsun (Turkmenistan)

    2009-10-15

    Breast metastases in cases leukemia are very rare and occur primarily in patients with acute myeloid leukemia. We report the involvement of breast metastases in a 30-year-old woman with acute T cell lymphoblastic leukemia. The patient's mammograms revealed an extremely dense pattern with ill-defined, denser mass-like lesions in both breasts. A bilateral breast ultrasonographic evaluation revealed lobular-shaped and partly ill-defined hypoechoic masses with a multi-septated nodular (mottled) appearance.

  4. A rare case of acute lymphoblastic leukaemia with hemophilia A

    Directory of Open Access Journals (Sweden)

    John Biju

    2009-12-01

    Full Text Available Abstract A rare case of Acute lymphoblastic leukemia with hemophillia in a 12 year old boy is presented in the article. Patient was known case of hemophillia (factor VIII deficiency. He was diagnosed as a case of ALL based on bone marrow examination and immunophenotypic study. Patient was treated as per Children Cancer group guidelines. The main aim of reporting this rare association lies in developing treatment strategies in preventing life threatening bleeding due to this rare association which though may be accidental but need further research.

  5. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...... and 2007. RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival...

  6. Pyomyositis During Induction Chemotherapy for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Kai-Liang Kao

    2006-04-01

    Full Text Available Herein, we report on the correct diagnosis and effective treatment procedures for pyomyositis, a very rare complication that remains a diagnostic challenge in children being treated for acute lymphoblastic leukemia (ALL. We report the case of a 10-year-old girl suffering from pyomyositis with ALL. Correct diagnosis is usually delayed because the initial symptom of pyomyositis, usually local pain, is similar to the common side effect of vincristine, a drug necessary for ALL induction therapy. We summarize the procedures taken to reach a timely diagnosis and therapeutic success.

  7. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2012-02-01

    Esophageal stricture is a rare complication of paediatric cancer treatment that usually occurs after esophageal exposure to radiotherapy. We describe 4 cases of esophageal stricture during chemotherapy for acute lymphoblastic leukemia. All patients presented with refractory vomiting and were diagnosed with radiologic contrast studies. None of the patients had received radiotherapy. Esophageal candidiasis was seen in 2 patients but the remaining 2 patients had earlier systemic candidiasis. High-dose dexamethasone may predispose these children to both esophageal candidiasis and peptic esophagitis. The etiology of esophageal strictures during treatment for acute leukemia is likely to be multifactorial but systemic candidiasis may play a significant role.

  8. Seasonal Variation of the Glycogen Enzyme Activity in Diploid and Triploid Pacific Oyster Gonad During Sexual Maturation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The glycogen content and the activities of two key enzymes in glycogen metabolism, glycogen phosphorylase and glycogen synthetase, in the gonad of diploid and triploid Pacific oysters (Crassostrea gigas) were compared during maturation. The glycogen content in the gonad of diploids decreased with gametogenesis (by 85.7%), but the glycogen content in the gonad of triploids did not vary significantly. Activity of glycogen phosphorylase (GP) in the gonad of diploids decreased with gametogenesis (by 55.5%), while GP activity of triploids did not vary significantly during maturation. Activity of glycogen synthetase (GS) in the gonad of diploids increased slightly with gametogenesis, reaching a peak in June. Activity of GS declined sharply from June to July, which might be due to gonad spawning. GS activity of triploid oysters in spawning time (July and August) was significantly higher than that

  9. A comparison of biomarker responses in juvenile diploid and triploid African catfish, Clarias gariepinus, exposed to the pesticide butachlor

    Science.gov (United States)

    Influence of waterborne butachlor (BUC), a commonly used pesticide, on morphometric, biochemical, and molecular biomarkers was evaluated in juvenile, full sibling, diploid and triploid African catfish (Clarias gariepinus). Fish were exposed for 21 days to one of three concentrati...

  10. Heat-shock-induced tetraploid and diploid/tetraploid mosaic in pond loach, Misgurnus anguillicaudatus

    OpenAIRE

    Fujimoto, Takafumi; Sakao, Suzu; Oshima, Kouzou; Yamaha, Etsuro; Arai, Katsutoshi

    2013-01-01

    Tetraploid fish, which are considered as key resources of diploid gametes for further breeding and ploidy manipulation, can be artificially induced by inhibition of the mitotic cell division with hydrostatic pressure or temperature treatments. Although many attempts have been made to induce artificial tetraploid strains, successful establishment of viable and fertile tetraploid strains are rare. In pond loach, Misgurnus anguillicaudatus, natural tetraploid individuals are distributed in wild ...

  11. Sequence Divergence of Microsatellites and Phylogeny Analysis in Tetraploid Cotton Species and Their Putative Diploid Ancestors

    Institute of Scientific and Technical Information of China (English)

    Wang-Zhen GUO; Dong FANG; Wen-Duo YU; Tian-Zhen ZHANG

    2005-01-01

    To determine the level of microsatellite sequence differences and to use the information to construct a phylogenetic relationship for cultivated tetraploid cotton (Gossypium spp.) species and their putative diploid ancestors, 10 genome-derived microsatellite primer pairs were used to amplify eight species,including two tetraploid and six diploid species, in Gossypium. A total of 92 unique amplicons were resolved using polyacrylamide gel electrophoresis. Each amplicon was cloned, sequenced, and analyzed using standard phylogenetic software. Allelic diversities were caused mostly by changes in the number of simple sequence repeat (SSR) motif repeats and only a small proportion resulted from interruption of the SSR motif within the locus for the same genome. The frequency of base substitutions was 0.5%-1.0% in different genomes, with only few indels found. Based on the combined 10 SSR flanking sequence data, the homology of A-genome diploid species averaged 98.9%, even though most of the amplicons were of the same size, and the sequence homology between G. gossypioides (Ulbr.) Standl. and three other D-genome species (G.raimondii Ulbr., G. davidsonii Kell., and G. thurberi Tod.) was 98.5%, 98.6%, and 98.5%, respectively.Phylogenetic trees of the two allotetraploid species and their putative diploid progenitors showed that homoelogous sequences from the A- and D-subgenome were still present in the polyploid subgenomes and they evolved independently. Meanwhile, homoelogous sequence interaction that duplicated loci in the polyploid subgenomes became phylogenetic sisters was also found in the evolutionary history of tetraploid cotton species. The results of the present study suggest that evaluation of SSR variation at the sequence level can be effective in exploring the evolutionary relationships among Gossypuim species.

  12. Differential gene expression and alternative splicing between diploid and tetraploid watermelon.

    Science.gov (United States)

    Saminathan, Thangasamy; Nimmakayala, Padma; Manohar, Sumanth; Malkaram, Sridhar; Almeida, Aldo; Cantrell, Robert; Tomason, Yan; Abburi, Lavanya; Rahman, Mohammad A; Vajja, Venkata G; Khachane, Amit; Kumar, Brajendra; Rajasimha, Harsha K; Levi, Amnon; Wehner, Todd; Reddy, Umesh K

    2015-03-01

    The exploitation of synthetic polyploids for producing seedless fruits is well known in watermelon. Tetraploid progenitors of triploid watermelon plants, compared with their diploid counterparts, exhibit wide phenotypic differences. Although many factors modulate alternative splicing (AS) in plants, the effects of autopolyploidization on AS are still unknown. In this study, we used tissues of leaf, stem, and fruit of diploid and tetraploid sweet watermelon to understand changes in gene expression and the occurrence of AS. RNA-sequencing analysis was performed along with reverse transcription quantitative PCR and rapid amplification of cDNA ends (RACE)-PCR to demonstrate changes in expression and splicing. All vegetative tissues except fruit showed an increased level of AS in the tetraploid watermelon throughout the growth period. The ploidy levels of diploids and the tetraploid were confirmed using a ploidy analyser. We identified 5362 and 1288 genes that were up- and downregulated, respectively, in tetraploid as compared with diploid plants. We further confirmed that 22 genes underwent AS events across tissues, indicating possibilities of generating different protein isoforms with altered functions of important transcription factors and transporters. Arginine biosynthesis, chlorophyllide synthesis, GDP mannose biosynthesis, trehalose biosynthesis, and starch and sucrose degradation pathways were upregulated in autotetraploids. Phloem protein 2, chloroplastic PGR5-like protein, zinc-finger protein, fructokinase-like 2, MYB transcription factor, and nodulin MtN21 showed AS in fruit tissues. These results should help in developing high-quality seedless watermelon and provide additional transcriptomic information related to other cucurbits. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Number of nucleoli in diploids and polyploids of the genus Achillea L.

    Directory of Open Access Journals (Sweden)

    Janina Dąbrowska

    2014-01-01

    Full Text Available Nucleoli were counted in 9228 interphase nuclei of the apical root meristem of 40 Achillea L. taxa (di-, tetra-. hexa- and octoploids. It was established that the distribution of nucleoli number in an interphase nucleus can be used as a rough practical indicator to distinguish between diploids and polyploids. The highest number of nucleoli (12 was found in an octoploid Achillea pannonica, but only in a small percentage of the nuclei (0.3% out of 283 nuclei.

  14. Genetic Load in Sexual and Asexual Diploids: Segregation, Dominance and Genetic Drift

    OpenAIRE

    Haag, Christoph R.; Roze, Denis

    2007-01-01

    In diploid organisms, sexual reproduction rearranges allelic combinations between loci (recombination) as well as within loci (segregation). Several studies have analyzed the effect of segregation on the genetic load due to recurrent deleterious mutations, but considered infinite populations, thus neglecting the effects of genetic drift. Here, we use single-locus models to explore the combined effects of segregation, selection, and drift. We find that, for partly recessive deleterious alleles...

  15. A comparative and experimental evaluation of performance of stocked diploid and triploid brook trout

    Science.gov (United States)

    Budy, Phaedra E.; Thiede, G.P.; Dean, A.; Olsen, D.; Rowley, G.

    2012-01-01

    Despite numerous negative impacts, nonnative trout are still being stocked to provide economically and socially valuable sport fisheries in western mountain lakes. We evaluated relative performance and potential differences in feeding strategy and competitive ability of triploid versus diploid brook trout Salvelinus fontinalis in alpine lakes, as well as behavioral and performance differences of diploid and triploid brook trout in two controlled experimental settings: behavioral experiments in the laboratory and performance evaluations in ponds. Across lakes, catch per unit effort (CPUE) and relative weight (Wr ) were not significantly different between ploidy levels. Mean sizes were also similar between ploidy levels except in two of the larger lakes where diploids attained slightly larger sizes (approximately 20 mm longer). We observed no significant differences between diploids and triploids in diet, diet preference, or trophic structure. Similarly, growth and condition did not differ between ploidy levels in smaller-scale pond experiments, and aggressive behavior did not differ between ploidy levels (fed or unfed fish trials) in the laboratory. Independent of ploidy level, the relative performance of brook trout varied widely among lakes, a pattern that appeared to be a function of lake size or a factor that covaries with lake size such as temperature regime or carrying capacity. In summary, we observed no significant differences in the relative performance of brook trout from either ploidy level across a number of indices, systems, and environmental conditions, nor any indication that one group is more aggressive or a superior competitor than the other. Collectively, these results suggest that triploid brook trout will offer a more risk-averse and promising management opportunity when they are stocked to these lakes and elsewhere to simultaneously meet the needs for the sport fishery and conservation objectives.

  16. 46,XX/69,XXX diploid-triploid mixoploidy with hypothyroidism and precocious puberty.

    OpenAIRE

    Järvelä, I E; Salo, M.K.; Santavuori, P.; Salonen, R K

    1993-01-01

    We report a 20 month old female patient with diploid-triploid mixoploidy (46,XX/69,XXX) syndrome with hypothyroidism and precocious puberty. The triploid cell line was only expressed in the fibroblast culture and comprised the majority (95%) of the cells. Chromosome analysis of the fetal blood sample and peripheral blood sample were normal. The patient shows typical features of full triploidy (growth and severe mental retardation, cranial and facial dysmorphism, complete syndactyly of fingers...

  17. TRANSPORTATION ISSUES FOR DECIDING WHEN TO DIPLOID A NEW DISTRIBUTION CENTER

    OpenAIRE

    MARCOS SINGER; PATRICIO DONOSO

    2000-01-01

    This work analyses the problem of defining when to diploid a new distribution center. The decision model considers the usual logistic cost drivers such as shipping, inventory, infrastructure and administration, focusing in the first one. The shipping cost driver is determined by the client coverage of the centers, which is calculated using a first order condition heuristic that takes into account the facilies' internal congestion. The model is applied to a company that operating in Santiago d...

  18. Re-analysis by fluorescence in situ hybridisation of spare embryos cultured until Day 5 after preimplantation genetic diagnosis for a 47, XYY infertile patient demonstrates a high incidence of diploid mosaic embryos: a case report.

    Science.gov (United States)

    Emiliani, S; Merino, E G; Van den Bergh, M; Abramowicz, M; Vassart, G; Englert, Y; Delneste, D

    2000-12-01

    Mosaicism in 4-8-cell human embryos analysed by fluorescence in situ hybridisation (FISH) has been widely reported, but few studies have addressed the incidence of mosaicism in more advanced embryonic stages. In the present study we analysed spare human embryos in a case of preimplantation genetic diagnosis (PGD) for increased risk of aneuploidy because of an infertile 47,XYY man. After replacement of two embryos typed as 1818XX at PGD, six spare embryos (not frozen because of their low quality) were re-analysed on Day 5 for PGD confirmation. Out of five embryos typed as 1818XY at PGD, four were diploid mosaic (DM) and one was normal in all cells. The sixth embryo, typed as 18XYY/1818181818X at PGD, was a DM. In spite of the bias of our small series of morphologically low-quality embryos, the surprisingly high proportion of mosaics (which confirms previous findings) questions the validity of PGD, but supports the strategy of transferring only the embryos where two blastomeres gave normal and concordant results at PGD. More data are required to understand the clinical significance of early diploid mosaicism (and its impact on implantation rate) and to determine whether some diploid mosaic embryos might be considered safe for transfer.

  19. Transcriptome Profile Analysis of Ovarian Tissues from Diploid and Tetraploid Loaches Misgurnus anguillicaudatus.

    Science.gov (United States)

    Luo, Weiwei; Liu, Chuanshu; Cao, Xiaojuan; Huang, Songqian; Wang, Weimin; Wang, Yeke

    2015-07-14

    RNA sequencing and short-read assembly was utilized to produce a transcriptome of ovarian tissues from three-year-old diploid and tetraploid loaches (Misgurnus anguillicaudatus). A total of 28,369 unigenes were obtained, comprising 10,546 unigenes with length longer than 1000 bp. More than 73% of the unigenes were annotated through sequence comparison with databases. The RNA-seq data revealed that 2253 genes were differentially expressed between diploid and tetraploid loaches, including 1263 up-regulated and 990 down-regulated genes in tetraploid loach. Some differentially expressed genes, such as vitellogenin (Vtg), gonadotropin releasing hormone receptor type A (GnRHRA), steroidogenic acute regulatory protein (StAR), mitogen-activated protein kinase 14a (MAPK14a), ATP synthase subunit alpha (atp5a), and synaptonemal complex protein 1 (Scp1), were involved in regulation of cell proliferation, division, gene transcription, ovarian development and energy metabolism, suggesting that these genes were related to egg diameter of the loach. Results of transcriptome profiling here were validated using real time quantitative PCR in ten selected genes. The present study provided insights into the transcriptome profile of ovarian tissues from diploid and tetraploid loaches Misgurnus anguillicaudatus, which was made available to the research community for functional genomics, comparative genomics, polyploidy evolution and molecular breeding of this loach and other related species.

  20. Comparative Small RNA Analysis of Pollen Development in Autotetraploid and Diploid Rice

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2016-04-01

    Full Text Available MicroRNAs (miRNAs play key roles in plant reproduction. However, knowledge on microRNAome analysis in autotetraploid rice is rather limited. Here, high-throughput sequencing technology was employed to analyze miRNAomes during pollen development in diploid and polyploid rice. A total of 172 differentially expressed miRNAs (DEM were detected in autotetraploid rice compared to its diploid counterpart, and 57 miRNAs were specifically expressed in autotetraploid rice. Of the 172 DEM, 115 and 61 miRNAs exhibited up- and down-regulation, respectively. Gene Ontology analysis on the targets of up-regulated DEM showed that they were enriched in transport and membrane in pre-meiotic interphase, reproduction in meiosis, and nucleotide binding in single microspore stage. osa-miR5788 and osa-miR1432-5p_R+1 were up-regulated in meiosis and their targets revealed interaction with the meiosis-related genes, suggesting that they may involve in the genes regulation associated with the chromosome behavior. Abundant 24 nt siRNAs associated with transposable elements were found in autotetraploid rice during pollen development; however, they significantly declined in diploid rice, suggesting that 24 nt siRNAs may play a role in pollen development. These findings provide a foundation for understanding the effect of polyploidy on small RNA expression patterns during pollen development that cause pollen sterility in autotetraploid rice.

  1. Genetic analysis of seedling resistance to crown rust in five diploid oat (Avena strigosa) accessions.

    Science.gov (United States)

    Cabral, A L; Park, R F

    2016-02-01

    Crown rust, caused by Puccinia coronata Corda f. sp. avenae Eriks., is a serious menace in oats, for which resistance is an effective means of control. Wild diploid oat accessions are a source of novel resistances that first need to be characterised prior to introgression into locally adapted oat cultivars. A genetic analysis of resistance to crown rust was carried out in three diverse diploid oat accessions (CIav6956, CIav9020, PI292226) and two cultivars (Saia and Glabrota) of A. strigosa. A single major gene conditioning resistance to Australian crown rust pathotype (Pt) 0000-2 was identified in each of the three accessions. Allelism tests suggested that these genes are either the same, allelic, or tightly linked with less than 1 % recombination. Similarly, a single gene was identified in Glabrota, and possibly two genes in Saia; both cultivars previously reported to carry two and three crown rust resistance genes, respectively. The identified seedling resistance genes could be deployed in combination with other resistance gene(s) to enhance durability of resistance to crown rust in hexaploid oat. Current diploid and hexaploid linkage maps and molecular anchor markers (simple sequence repeat [SSR] and diversity array technology [DArT] markers) should facilitate their mapping and introgression into hexaploid oat.

  2. Transcriptome Profile Analysis of Ovarian Tissues from Diploid and Tetraploid Loaches Misgurnus anguillicaudatus

    Directory of Open Access Journals (Sweden)

    Weiwei Luo

    2015-07-01

    Full Text Available RNA sequencing and short-read assembly was utilized to produce a transcriptome of ovarian tissues from three-year-old diploid and tetraploid loaches (Misgurnus anguillicaudatus. A total of 28,369 unigenes were obtained, comprising 10,546 unigenes with length longer than 1000 bp. More than 73% of the unigenes were annotated through sequence comparison with databases. The RNA-seq data revealed that 2253 genes were differentially expressed between diploid and tetraploid loaches, including 1263 up-regulated and 990 down-regulated genes in tetraploid loach. Some differentially expressed genes, such as vitellogenin (Vtg, gonadotropin releasing hormone receptor type A (GnRHRA, steroidogenic acute regulatory protein (StAR, mitogen-activated protein kinase 14a (MAPK14a, ATP synthase subunit alpha (atp5a, and synaptonemal complex protein 1 (Scp1, were involved in regulation of cell proliferation, division, gene transcription, ovarian development and energy metabolism, suggesting that these genes were related to egg diameter of the loach. Results of transcriptome profiling here were validated using real time quantitative PCR in ten selected genes. The present study provided insights into the transcriptome profile of ovarian tissues from diploid and tetraploid loaches Misgurnus anguillicaudatus, which was made available to the research community for functional genomics, comparative genomics, polyploidy evolution and molecular breeding of this loach and other related species.

  3. Parasexual genetics of Dictyostelium gene disruptions: identification of a ras pathway using diploids

    Directory of Open Access Journals (Sweden)

    Insall Robert H

    2003-07-01

    Full Text Available Abstract Background The relative ease of targeted gene disruption in the social amoeba Dictyostelium has stimulated its widespread use as an experimental organism for cell and developmental biology. However, the field has been hamstrung by the lack of techniques to recombine disrupted genes. Results We describe new techniques for parasexual fusion of strains in liquid medium, selection and maintenance of the resulting stable diploid strains, and segregation to make recombined haploids. We have used these techniques to isolate rasS/gefB double nulls. The phenotypes of these mutants are no more severe than either parent, with movement, phagocytosis and fluid-phase endocytosis affected to the same degree as in rasS or gefB single nulls. In addition, we have produced diploids from one AX2- and one AX3-derived parent, providing an axenic strain with fewer secondary phenotypes than has been previously available. Conclusions The phenotype of the rasS/gefB double mutant suggests that the RasS and GefB proteins lie on the same linear pathway. In addition, axenic diploids and the techniques to generate, maintain and segregate them will be productive tools for future work on Dictyostelium. They will particularly facilitate generation of multiple mutants and manuipulation of essential genes.

  4. A Distinct Endogenous Pararetrovirus Family in Nicotiana tomentosiformis, a Diploid Progenitor of Polyploid Tobacco1[w

    Science.gov (United States)

    Gregor, Wolfgang; Mette, M. Florian; Staginnus, Christina; Matzke, Marjori A.; Matzke, Antonius J.M.

    2004-01-01

    A distinct endogenous pararetrovirus (EPRV) family corresponding to a previously unknown virus has been identified in the genome of Nicotiana tomentosiformis, a diploid ancestor of allotetraploid tobacco (Nicotiana tabacum). The putative virus giving rise to N. tomentosiformis EPRVs (NtoEPRVs) is most similar to tobacco vein clearing virus, an episomal form of a normally silent EPRV family in Nicotiana glutinosa; it is also related to a putative virus giving rise to the NsEPRV family in Nicotiana sylvestris (the second diploid progenitor of tobacco) and in the N. sylvestris fraction of the tobacco genome. The copy number of NtoEPRVs is significantly higher in N. tomentosiformis than in tobacco. This suggests that after the polyploidization event, many copies were lost from the polyploid genome or were accumulated specifically in the diploid genome. By contrast, the copy number of NsEPRVs has remained constant in N. sylvestris and tobacco, indicating that changes have occurred preferentially in the NtoEPRV family during evolution of the three Nicotiana species. NtoEPRVs are often flanked by Gypsy retrotransposon-containing plant DNA. Although the mechanisms of NtoEPRV integration, accumulation, and/or elimination are unknown, these processes are possibly linked to retrotransposon activity. PMID:14988473

  5. Drought stress-induced changes of microRNAs in diploid and autotetraploid Paulownia tomentosa.

    Science.gov (United States)

    Cao, Xibing; Fan, Guoqiang; Cao, Lin; Deng, Minjie; Zhao, Zhenli; Niu, Suyan; Wang, Zhe; Wang, Yuanlong

    2017-01-01

    Drought stress adversely affects plant productivity. Growth and timber production of Paulownia trees are limited under drought stress. Changes in gene expression patterns and miRNA in different ploidy of Paulownia tomentosa have been investigated. However, the responses of P. tomentosa to drought stress at the microRNA (miRNA) level have not been reported so far. To identify miRNA candidates and their target genes involved in the drought stress response in diploid and tetraploid P. tomentosa, four small RNA and four degradome libraries from diploid and autotetraploid P. tomentosa under normal and drought stress conditions were constructed and sequenced. A total of 41 conserved and 90 novel miRNAs were identified. Among these miRNAs, 67 (26 conserved and 41 novel) and 53 (six conserved and 47 novel) were significantly differentially expressed in response to drought stress in diploid and autotetraploid P. tomentosa, respectively. Degradome analysis identified 356 candidate miRNA target genes that encoded proteins with functions that included plant defense, transcriptional regulation, and hormone metabolism. In particular, miR4 and miR156 were identified only in autotetraploid P. tomentosa under drought stress. These results will help us build a foundation for future studies of the biological functions of miRNA-mediated gene regulation in P. tomentosa.

  6. Cryptic fitness advantage: diploids invade haploid populations despite lacking any apparent advantage as measured by standard fitness assays.

    Directory of Open Access Journals (Sweden)

    Aleeza C Gerstein

    Full Text Available Ploidy varies tremendously within and between species, yet the factors that influence when or why ploidy variants are adaptive remains poorly understood. Our previous work found that diploid individuals repeatedly arose within ten replicate haploid populations of Saccharomyces cerevisiae, and in each case we witnessed diploid takeover within ~1800 asexual generations of batch culture evolution in the lab. The character that allowed diploids to rise in frequency within haploid populations remains unknown. Here we present a number of experiments conducted with the goal to determine what this trait (or traits might have been. Experiments were conducted both by sampling a small number of colonies from the stocks frozen every two weeks (~ 93 generations during the original experiment, as well through sampling a larger number of colonies at the two time points where polymorphism for ploidy was most prevalent. Surprisingly, none of our fitness component measures (lag phase, growth rate, biomass production indicated an advantage to diploidy. Similarly, competition assays against a common competitor and direct competition between haploid and diploid colonies isolated from the same time point failed to indicate a diploid advantage. Furthermore, we uncovered a tremendous amount of trait variation among colonies of the same ploidy level. Only late-appearing diploids showed a competitive advantage over haploids, indicating that the fitness advantage that allowed eventual takeover was not diploidy per se but an attribute of a subset of diploid lineages. Nevertheless, the initial rise in diploids to intermediate frequency cannot be explained by any of the fitness measures used; we suggest that the resolution to this mystery is negative frequency-dependent selection, which is ignored in the standard fitness measures used.

  7. Factors influencing distribution and local coexistence of diploids and tetraploids of Vicia cracca: inferences from a common garden experiment.

    Science.gov (United States)

    Eliášová, Anežka; Münzbergová, Zuzana

    2017-07-01

    Vicia cracca diploids and autotetraploids are highly parapatric in Europe; tetraploids reside in western and northern part, whereas diploids occupy much drier south-eastern part. They meet together in a Central European contact zone. This distribution pattern raised questions about a transformative effect of polyploidization on plant performance and environmental tolerances. We investigated plant survival, growth, and seed production in two water regimes in a common garden experiment using seeds collected from five localities in the Central European contact zone where diploids and tetraploids occur in sympatry. Obtained data imply that tetraploids of V. cracca are not generally superior in performance to diploids. Significantly larger seeds from tetraploid mother plants collected in the field were not correlated with greater stature of the seedlings. Nonetheless, tetraploids might have a potential to out-compete diploids in the long run due to the tetraploids' ability of greater growth which manifested in the second year of cultivation. Considering the response of diploids and tetraploids to water supply, drought stressed tetraploids but not diploids produced a higher proportion of aborted seeds than watered ones, which implies that tetraploids are more drought susceptible than diploids. On the other hand, decreased plant height in drought stresses tetraploids, which simultaneously increased total seed production, may suggest that tetraploids have a greater ability to avoid local extinction under unfavourable conditions by enhancing biomass allocation into production of seeds at the cost of lower growth. The significant interaction between ploidy level and locality in several traits suggests possible polyfyletic origin of tetraploids and the necessity to clarify the history of the tetraploids in Europe.

  8. Conditions in home and transplant soils have differential effects on the performance of diploid and allotetraploid anthericum species.

    Directory of Open Access Journals (Sweden)

    Lucie Černá

    Full Text Available Due to increased levels of heterozygosity, polyploids are expected to have a greater ability to adapt to different environments than their diploid ancestors. While this theoretical pattern has been suggested repeatedly, studies comparing adaptability to changing conditions in diploids and polyploids are rare. The aim of the study was to determine the importance of environmental conditions of origin as well as target conditions on performance of two Anthericum species, allotetraploid A. liliago and diploid A. ramosum and to explore whether the two species differ in the ability to adapt to these environmental conditions. Specifically, we performed a common garden experiment using soil from 6 localities within the species' natural range, and we simulated the forest and open environments in which they might occur. We compared the performance of diploid A. ramosum and allotetraploid A. liliago originating from different locations in the different soils. The performance of the two species was not affected by simulated shading but differed strongly between the different target soils. Growth of the tetraploids was not affected by the origin of the plants. In contrast, diploids from the most nutrient poor soil performed best in the richest soil, indicating that diploids from deprived environments have an increased ability to acquire nutrients when available. They are thus able to profit from transfer to novel nutrient rich environments. Therefore, the results of the study did not support the general expectation that the polyploids should have a greater ability than the diploids to adapt to a wide range of conditions. In contrast, the results are in line with the observation that diploids occupy a wider range of environments than the allotetraploids in our system.

  9. Conditions in home and transplant soils have differential effects on the performance of diploid and allotetraploid anthericum species.

    Science.gov (United States)

    Černá, Lucie; Münzbergová, Zuzana

    2015-01-01

    Due to increased levels of heterozygosity, polyploids are expected to have a greater ability to adapt to different environments than their diploid ancestors. While this theoretical pattern has been suggested repeatedly, studies comparing adaptability to changing conditions in diploids and polyploids are rare. The aim of the study was to determine the importance of environmental conditions of origin as well as target conditions on performance of two Anthericum species, allotetraploid A. liliago and diploid A. ramosum and to explore whether the two species differ in the ability to adapt to these environmental conditions. Specifically, we performed a common garden experiment using soil from 6 localities within the species' natural range, and we simulated the forest and open environments in which they might occur. We compared the performance of diploid A. ramosum and allotetraploid A. liliago originating from different locations in the different soils. The performance of the two species was not affected by simulated shading but differed strongly between the different target soils. Growth of the tetraploids was not affected by the origin of the plants. In contrast, diploids from the most nutrient poor soil performed best in the richest soil, indicating that diploids from deprived environments have an increased ability to acquire nutrients when available. They are thus able to profit from transfer to novel nutrient rich environments. Therefore, the results of the study did not support the general expectation that the polyploids should have a greater ability than the diploids to adapt to a wide range of conditions. In contrast, the results are in line with the observation that diploids occupy a wider range of environments than the allotetraploids in our system.

  10. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.

    Science.gov (United States)

    Bacher, Nicole; Tiefenthaler, Martin; Sturm, Sonja; Stuppner, Hermann; Ausserlechner, Michael J; Kofler, Reinhard; Konwalinka, Günther

    2006-03-01

    Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.

  11. Comparing sex steroid levels during the annual cycles of rainbow trout (Oncorhynchus mykiss) diploid female (XX) and triploid female (XXX) genotypic sex.

    Science.gov (United States)

    Espinosa, E; Josa, A; Gil, L; Malo, C; Mitjana, O

    2013-02-01

    In this study, the annual cycle of the gonadal steroids testosterone (T), 11-ketotestosterone (11-KT), 17β-estradiol (E2) and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) was determined using radioimmunoassay and then compared for two populations of rainbow trout, XX diploid females (n = 40) and XXX triploid females (n = 15). In females, E2 and DHP levels were found to be significantly related to body weight (r = 0.22513; p 0.001, respectively). In this group, E2 concentrations peaked in November (25.05 ng/ml), while maximum DHP levels, only measurable from October to April, were attained in February (64.14 ng/ml). No significant differences in hormone ranges related to egg output ability were observed. Finally, sex steroid concentrations were low in the triploid female XXX fish compared to the female XX population. Nevertheless, maximum T (33.85 ng/ml) and 11-KT (32.35 ng/ml) levels were recorded in January, for XXX. The levels for these two hormones are relatively high and are also significantly associated (r = 0.8430; p < 0.0001). Diploid females showed significantly higher levels of E2 than triploids over the 12-month study period. The female triploid fish produced the lowest steroid hormone levels, such that these would be the most suitable for human consumption.

  12. Erythrocyte heat shock protein responses to chronic (in vivo) and acute (in vitro) temperature challenge in diploid and triploid salmonids.

    Science.gov (United States)

    Saranyan, Pillai V; Ross, Neil W; Benfey, Tillmann J

    2017-04-01

    This research investigated how ploidy level (diploid versus triploid) affects the heat shock protein (HSP) response in erythrocytes under different thermal stress regimes, both in vivo and in vitro, in Atlantic salmon (Salmo salar) and brook charr (Salvelinus fontinalis) in order to address the question of why triploids typically have reduced thermal tolerance. A preliminary study confirmed that identical volumes of diploid and triploid erythrocytes (which equates to a smaller number of larger cells for triploids compared to diploids) did not differ in total protein synthesis rates. After chronic (100d) acclimation of fish to 5, 15 and 25°C, triploid erythrocytes had lower HSP70, HSP90, heat shock factor 1 (HSF1) and ubiquitin (free and total) levels than diploids in both species. Furthermore, Atlantic salmon erythrocytes showed significantly higher protein breakdown (based on conjugated ubiquitin levels) in triploids than diploids after acute heat stress in vitro, but no significant difference was detected between ploidies after acute cold stress. These results indicate that: 1) triploid erythrocytes synthesize more total protein per cell than diploids as a result of increased cell size; 2) triploids have sufficient total HSP levels for survival under low stress conditions; and 3) the lower basal titres of HSPs in triploids may be a handicap when combating acute stress. Taken together, this suggests that triploids are limited in their ability to withstand thermal stress because of a reduced ability to maintain proteostasis under stressful conditions.

  13. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

  14. MR features of isolated uterine relapse in an adolescent with acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Novellas, Sebastien; Fournol, Maude; Geoffray, Anne; Chevallier, Patrick [Regional Hospital Centre and University of Nice, Medical Imaging Service, Archet 2 Hospital, 151 route de Saint Antoine de Ginestiere, B.P. 3079, Nice Cedex 3 (France); Deville, Anne [Regional Hospital Centre and University of Nice, Paediatric Service, Archet 2 Hospital, Nice (France); Kurzenne, Jean-Yves [Regional Hospital Centre and University of Nice, Paediatric Surgery Service, Archet 2 Hospital, Nice (France)

    2008-03-15

    Relapses of lymphoblastic leukaemia traditionally involve the central nervous system and testes in boys. Involvement of the female pelvic organs is frequently found at autopsy; however, involvement of the cervical uterus is rare and even less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old adolescent with a history of lymphoblastic leukaemia during childhood. Pelvic MRI was the best tool to assess the size, characteristics and invasive nature of this lesion of the uterine cervix. To our knowledge, this is a unique case in that we describe the MRI appearance of a relapsing lymphoblastic leukaemic mass both before and after treatment. (orig.)

  15. Genomic effects on advertisement call structure in diploid and triploid hybrid waterfrogs (Anura, Pelophylax esculentus)

    Science.gov (United States)

    2013-01-01

    Background In anurans, differences in male mating calls have intensively been studied with respect to taxonomic classification, phylogeographic comparisons among different populations and sexual selection. Although overall successful, there is often much unexplained variation in these studies. Potential causes for such variation include differences among genotypes and breeding systems, as well as differences between populations. We investigated how these three factors affect call properties in male water frogs of Pelophylax lessonae (genotype LL), P. ridibundus (RR) and their interspecific hybrid P. esculentus which comes in diploid (LR) and triploid types (LLR, LRR). Results We investigated five call parameters that all showed a genomic dosage effect, i.e. they either decreased or increased with the L/R ratio in the order LL-LLR-LR-LRR-RR. Not all parameters differentiated equally well between the five genotypes, but combined they provided a good separation. Two of the five call parameters were also affected by the breeding system. Calls of diploid LR males varied, depending on whether these males mated with one or both of the parental species (diploid systems) or triploid hybrids (mixed ploidy systems). With the exception of the northernmost mixed-ploidy population, call differences were not related to the geographic location of the population and they were not correlated with genetic distances in the R and L genomes. Conclusions We found an influence of all three tested factors on call parameters, with the effect size decreasing from genotype through breeding system to geographic location of the population. Overall, results were in line with predictions from a dosage effect in L/R ratios, but in three call parameters all three hybrid types were more similar to one or the other parental species. Also calls of diploid hybrids varied between breeding systems in agreement with the sexual host required for successful reproduction. The lack of hybrid call differences

  16. Genomic effects on advertisement call structure in diploid and triploid hybrid waterfrogs (Anura, Pelophylax esculentus).

    Science.gov (United States)

    Hoffmann, Alexandra; Reyer, Heinz-Ulrich

    2013-12-04

    In anurans, differences in male mating calls have intensively been studied with respect to taxonomic classification, phylogeographic comparisons among different populations and sexual selection. Although overall successful, there is often much unexplained variation in these studies. Potential causes for such variation include differences among genotypes and breeding systems, as well as differences between populations. We investigated how these three factors affect call properties in male water frogs of Pelophylax lessonae (genotype LL), P. ridibundus (RR) and their interspecific hybrid P. esculentus which comes in diploid (LR) and triploid types (LLR, LRR). We investigated five call parameters that all showed a genomic dosage effect, i.e. they either decreased or increased with the L/R ratio in the order LL-LLR-LR-LRR-RR. Not all parameters differentiated equally well between the five genotypes, but combined they provided a good separation. Two of the five call parameters were also affected by the breeding system. Calls of diploid LR males varied, depending on whether these males mated with one or both of the parental species (diploid systems) or triploid hybrids (mixed ploidy systems). With the exception of the northernmost mixed-ploidy population, call differences were not related to the geographic location of the population and they were not correlated with genetic distances in the R and L genomes. We found an influence of all three tested factors on call parameters, with the effect size decreasing from genotype through breeding system to geographic location of the population. Overall, results were in line with predictions from a dosage effect in L/R ratios, but in three call parameters all three hybrid types were more similar to one or the other parental species. Also calls of diploid hybrids varied between breeding systems in agreement with the sexual host required for successful reproduction. The lack of hybrid call differences in a mixed-ploidy population at

  17. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Soosay Raj TA

    2013-11-01

    Full Text Available Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL, a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory–motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI] formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR–ABL1 (Ph-negative (Ph- disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+ and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.Keywords: vincristine sulfate liposomal injection, liposomes, sphingosomal vincristine, acute lymphoblastic leukemia, chemotherapy

  18. Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro.

    Science.gov (United States)

    Seifert, Georg; Jesse, Patrick; Laengler, Alfred; Reindl, Tobias; Lüth, Maria; Lobitz, Stephan; Henze, Günter; Prokop, Aram; Lode, Holger N

    2008-06-18

    Viscum album (Mistletoe) is one of the most widely used alternative cancer therapies. Aqueous mistletoe extracts (MT) contain the three mistletoe lectins I, II and III as one predominant group of biologically active agents. Although MT is widely used, there is a lack of scientifically sound preclinical and clinical data. In this paper, we describe for the first time the in vivo efficacy and mechanism of action of MT in lymphoblastic leukemia. For this purpose, we first investigated both the cytotoxic effect and the mechanism of action of two standardized aqueous MTs (MT obtained from fir trees (MT-A); MT obtained from pine trees (MT-P)) in a human acute lymphoblastic leukemia (ALL) cell line (NALM-6). MT-A, MT-P and ML-I inhibited cell proliferation as determined by Casy Count analysis at very low concentrations with MT-P being the most cytotoxic extract. DNA-fragmentation assays indicated that dose-dependent induction of apoptosis was the main mechanism of cell death. Finally, we evaluated the efficacy of MT-A and MT-P in an in vivo SCID-model of pre-B ALL (NALM-6). Both MTs significantly improved survival (up to 55.4 days) at all tested concentrations in contrast to controls (34.6 days) without side effects.

  19. High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma.

    Science.gov (United States)

    Del Principe, Maria Ilaria; Buccisano, Francesco; Cefalo, Mariagiovanna; Maurillo, Luca; Di Caprio, Luigi; Di Piazza, Fabio; Sarlo, Chiara; De Angelis, Gottardo; Irno Consalvo, Maria; Fraboni, Daniela; De Santis, Giovanna; Ditto, Concetta; Postorino, Massimiliano; Sconocchia, Giuseppe; Del Poeta, Giovanni; Amadori, Sergio; Venditti, Adriano

    2014-09-01

    Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %) samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos) patients showed a significantly shorter overall survival (OS) compared to CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p = 0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.

  20. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Hulleman, Esther; Kazemier, Karin M.; Holleman, Amy; VanderWeele, David J.; Rudin, Charles M.; Broekhuis, Mathilde J. C.; Evans, William E.; Pieters, Rob; Den Boer, Monique L.

    2009-01-01

    Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant pr

  1. Charcot-Marie-Tooth Disease in a Child with Acute Lymphoblastic ...

    African Journals Online (AJOL)

    ... with Acute Lymphoblastic Leukaemia: A Case Report and Review of Literature. ... vincristine treatment triggering the expression of asymptomatic CMT disease. ... Results: Facial nerve palsy, increasing lower extremities muscle weakness ...

  2. Charcot-Marie-Tooth Disease in a Child with Acute Lymphoblastic ...

    African Journals Online (AJOL)

    Alasia Datonye

    into vincristine therapy in a ten year old male on treatment for acute lymphoblastic ... diagnosis of malignancy to identify any undiagnosed neurologic deficits .... There is no cure for CMT, but physical therapy, occupational therapy, braces and ...

  3. Subdural hemorrhages in acute lymphoblastic leukemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Rui Yin; CaiXia Qiu; XiaoHui Dong; YeLong Chen

    2016-01-01

    Background:Acute lymphoblastic leukemia is a rare hematological malignancy.Pure subdural hemorrhages in a patient with acute lymphoblastic leukemia patient are extremely rare.Case presentation:This case presented acute spontaneous subdural hemorrhage without head trauma at first,and acute lymphoblastic leukemia was diagnosed later.The second time,the patient was admitted with multiple pure subdural hemorrhages in different locations and periods with a history of slight head trauma.Conclusions:Pure subdural hemorrhages can occur in a patient with acute lymphoblastic leukemia.More care would be needed for pure subdural hemorrhages without obvious head trauma,and patients with hematological malignancies should be protected from even mild head trauma.

  4. The controversy of varicella vaccination in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Caniza, Miguela A; Hunger, Stephen P; Schrauder, Andre

    2012-01-01

    The available guidelines for varicella vaccination of susceptible children with acute lymphoblastic leukemia (ALL) have become increasingly conservative. However, vaccination of those who have remained in continuous complete remission for 1 year and are receiving chemotherapy is still considered...

  5. Hepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Ebbesen, Maria S.; Nygaard, Ulrikka; Rosthøj, Susanne

    2017-01-01

    Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine...

  6. LncRNA Expression Discriminates Karyotype and Predicts Survival in B-lymphoblastic Leukemia

    Science.gov (United States)

    Fernando, Thilini R.; Rodriguez-Malave, Norma I.; Waters, Ella V.; Yan, Weihong; Casero, David; Basso, Giuseppe; Pigazzi, Martina; Rao, Dinesh S.

    2015-01-01

    Long non-coding RNAs (lncRNAs) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by RT-qPCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B-cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development. Implications lncRNA expression has the potential to segregate the common subtypes of B-ALL, predict the cytogenetic subtype, and indicate prognosis. PMID:25681502

  7. Incipient Genome Differentiation in Gossypium. III. Comparison of Chromosomes of G. HIRSUTUM and Asiatic Diploids Using Heterozygous Translocations.

    Science.gov (United States)

    Menzel, M Y; Hasenkampf, C A; Stewart, J M

    1982-01-01

    Hybrids between upland cotton (G. hirsutum, genome constitution 2A(h)D(h)) and either A-genome or D-genome diploid species exhibit 26 paired and 13 unpaired chromosomes at metaphase I. The A(h) and D(h) genomes are therefore considered homoeologous with those of the respective diploids. Previous studies, nevertheless, revealed a low level of ("incipient") differentiation between D(h) and various diploid D genomes. The diploid A genomes have been regarded as more closely homologous to A(h) on the basis of low preferential pairing and autotetraploid segregation ratios in allohexaploids.-The present study addressed the following questions: Are the diploid A genomes differentiated from A(h) in meiotic homology? If so, is the differentiation manifested equally by all 13 chromosomes or is it localized in certain chromosomes?-Three diploid A-genome lines representing G. herbaceum and G. arboreum were hybridized by in ovulo culture of embryos (1) with a standard line of G. hirsutum, which differs from G. herbaceum by two and from G. arboreum by three naturally occurring reciprocal translocations involving chromosomes 1-5, and (2) with six lines homozygous for experimental translocations involving chromosomes 6, 7, 10, 11, 12 and 13. Chiasma frequencies in hybrids were compared with those in appropriate G. hirsutum controls. In every comparison overall chiasma frequencies were slightly lower in the hybrids. Therefore A(h) appears to be differentiated from the diploid A genomes. No localized differentiation was detected in chromosomes marked by experimental translocations. The differentiation may be localized mainly in chromosomes 4 and 5.

  8. Effect of ploidy increase on transgene expression: example from Citrus diploid cybrid and allotetraploid somatic hybrid expressing the EGFP gene.

    Science.gov (United States)

    Xu, Shi-Xiao; Cai, Xiao-Dong; Tan, Bin; Li, Ding-Li; Guo, Wen-Wu

    2011-07-01

    Polyploidization is an important speciation mechanism for all eukaryotes, and it has profound impacts on biodiversity dynamics and ecosystem functioning. Green fluorescent protein (GFP) has been used as an effective marker to visually screen somatic hybrids at an early stage in protoplast fusion. We have previously reported that the intensity of GFP fluorescence of regenerated embryoids was also an early indicator of ploidy level. However, little is known concerning the effects of ploidy increase on the GFP expression in citrus somatic hybrids at the plant level. Herein, allotetraploid and diploid cybrid plants with enhanced GFP (EGFP) expression were regenerated from the fusion of embryogenic callus protoplasts from 'Murcott' tangor (Citrus reticulata Blanco × Citrus sinensis (L.) Osbeck) and mesophyll protoplasts from transgenic 'Valencia' orange (C. sinensis (L.) Osbeck) expressing the EGFP gene, via electrofusion. Subsequent simple sequence repeat (SSR), chloroplast simple sequence repeat and cleaved amplified polymorphic sequence analysis revealed that the two regenerated tetraploid plants were true allotetraploid somatic hybrids possessing nuclear genomic DNA of both parents and cytoplasmic DNA from the callus parent, while the five regenerated diploid plants were cybrids containing nuclear DNA of the leaf parent and with complex segregation of cytoplasmic DNA. Furthermore, EGFP expression was compared in cells and protoplasts from mature leaves of these diploid cybrids and allotetraploid somatic hybrids. Results showed that the intensity of GFP fluorescence per cell or protoplast in diploid was generally brighter than in allotetraploid. Moreover, same hybridization signal was detected on allotetraploid and diploid plants by Southern blot analysis. By real-time RT-PCR and Western blot analysis, GFP expression level of the diploid cybrid was revealed significantly higher than that of the allotetraploid somatic hybrid. These results suggest that ploidy

  9. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06–27.17; odds ratio=6.86, 95% confidence interval, 1.86–25.26, respectively). CCR7 expression in the upper fourth quartile correlated with

  10. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  11. [Tumor lysis syndrome in a pregnancy complicated with acute lymphoblastic leukemia].

    Science.gov (United States)

    Álvarez-Goris, M P; Sánchez-Zamora, R; Torres-Aguilar, A A; Briones Garduño, J C

    2016-04-01

    Acute leukemia is rare during pregnancy, affects about 1 in 75,000 pregnancies, of all leukemias diagnosed only 28% are acute lymphoblastic leukemia, this is a risk factor to develop spontaneous tumor lysis syndrome, it's a oncologic complication potentially deadly if the prophylactic treatment its avoided. Cases of acute lymphoblastic leukemia associated with pregnancy has been poorly documented in the literature the association of these two entities to pregnancy is the first report published worldwide, so the information is limited.

  12. Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2013-08-01

    Full Text Available The central nervous system is the most commonly affected extramedullary site in acute lymphoblastic leukemia. Although morphologic evaluation of the cerebrospinal fluid has been traditionally used for diagnosing central nervous system involvement, it is a method of low sensitivity. The present study aimed at evaluating the use of immunophenotyping in the detection of blasts in the cerebrospinal fluid from children and adolescents with acute lymphoblastic leukemia.

  13. Acute lymphoblastic leukemia of childhood presenting as aplastic anemia: report of two cases

    Directory of Open Access Journals (Sweden)

    Laura Villarreal-Martínez

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia is the most common malignancy in pediatric patients; its diagnosis is usually easy to establish as malignant lymphoblasts invade the bone marrow and peripheral blood. Some acute lymphoblastic leukemia patients may initially present with pancytopenia and a hypoplastic bone marrow leading to the initial diagnosis of aplastic anemia. In most of these patients clinical improvement occurs, with normalization of the complete blood count within six months, although recovery can also develop a few weeks after initiating steroid therapy. The etiologic relationship between the aplastic anemia features and the subsequent overt development of acute lymphoblastic leukemia has not been established. We describe the cases of two children who presented with severe infection and signs and symptoms of aplastic anemia confirmed by bone marrow aspirate and bone marrow biopsy that developed acute lymphoblastic leukemia thereafter. No specific therapy for aplastic anemia was administered, nevertheless a full spontaneous recovery was observed in both cases. Acute lymphoblastic leukemia was successfully treated with standard chemotherapy, both children remaining in complete remission 16 and 17 months after their initial aplastic anemia diagnosis.

  14. Field evaluation of in vitro-induced tetraploid and diploid Centella asiatica (L.) Urban.

    Science.gov (United States)

    Thong-On, Wachiraporn; Arimatsu, Panida; Pitiporn, Supaporn; Soonthornchareonnon, Noppamas; Prathanturarug, Sompop

    2014-04-01

    Centella asiatica-a medicinal plant that produces high-value active triterpenoids-is in increasing demand by the pharmaceutical and cosmetic industries. The aim of this study was to field-test one induced tetraploid and three diploid C. asiatica lines for the selection of high-quality plants with high phytomass and triterpenoid content and to determine their optimal harvesting time. All tested C. asiatica were micropropagated using an established protocol. One-month-old plantlets were acclimatized for the field experiment. The plants were grown in a randomized complete block design (RCBD) with three replications, ten plantlets per replication, and the experimental bed site was 0.6 × 1.0 m. Growth parameters, phytomass and the amounts of four active triterpenoids were evaluated. All lines exhibited the highest growth, yields and triterpenoids at 4 months after cultivation. The tetraploid line showed significantly better characteristics, i.e., larger leaf area, leaf width, petiole length, and greater yields, than diploid lines. Dry weight per cultivated area (77.53 ± 3.07 g/m(2)) and total triterpenoids (15.38 ± 0.76 % dry weight) were increased significantly in tetraploid plants of C. asiatica. Furthermore, the harvesting time had an effect on the yield and triterpenoid content (P tetraploid and diploid lines, the yields and triterpenoid content per cultivated area reached their maximum at 4 months after planting. Our results demonstrated that polyploidy induction is a beneficial tool that can be used to improve the medicinal value of C. asiatica.

  15. The baker's yeast diploid genome is remarkably stable in vegetative growth and meiosis.

    Directory of Open Access Journals (Sweden)

    K T Nishant

    2010-09-01

    Full Text Available Accurate estimates of mutation rates provide critical information to analyze genome evolution and organism fitness. We used whole-genome DNA sequencing, pulse-field gel electrophoresis, and comparative genome hybridization to determine mutation rates in diploid vegetative and meiotic mutation accumulation lines of Saccharomyces cerevisiae. The vegetative lines underwent only mitotic divisions while the meiotic lines underwent a meiotic cycle every ∼20 vegetative divisions. Similar base substitution rates were estimated for both lines. Given our experimental design, these measures indicated that the meiotic mutation rate is within the range of being equal to zero to being 55-fold higher than the vegetative rate. Mutations detected in vegetative lines were all heterozygous while those in meiotic lines were homozygous. A quantitative analysis of intra-tetrad mating events in the meiotic lines showed that inter-spore mating is primarily responsible for rapidly fixing mutations to homozygosity as well as for removing mutations. We did not observe 1-2 nt insertion/deletion (in-del mutations in any of the sequenced lines and only one structural variant in a non-telomeric location was found. However, a large number of structural variations in subtelomeric sequences were seen in both vegetative and meiotic lines that did not affect viability. Our results indicate that the diploid yeast nuclear genome is remarkably stable during the vegetative and meiotic cell cycles and support the hypothesis that peripheral regions of chromosomes are more dynamic than gene-rich central sections where structural rearrangements could be deleterious. This work also provides an improved estimate for the mutational load carried by diploid organisms.

  16. Improved stress resistance and ethanol production by segmental haploidization of the diploid genome in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kaboli, Saeed; Miyamoto, Tetsuya; Sunada, Keisuke; Sasano, Yu; Sugiyama, Minetaka; Harashima, Satoshi

    2016-06-01

    Saccharomyces cerevisiae strains from industrial and natural geographical environments are reported to show great variation in copy number of chromosomal regions. Such variation contributes to the mechanisms underlying adaptation to different environments. Here, we created and phenotypically analyzed segmentally haploidized strains, each harboring a deletion of one copy of approximately 100-300 kb of the left or right terminal region of 16 chromosomes in a diploid strain by using a PCR-mediated chromosomal deletion method. No haploidized strain of the 158-kb deleted right terminal region of chromosome III or the 172-kb deleted right terminal region of chromosome VI was produced; however, segmentally haploidized strains of the remaining 30 terminal regions were obtained. Among these 30 strains, two exhibited higher lactic acid resistance and two displayed higher thermo-tolerance at 41°C versus the host diploid strain. By contrast, four and two segmentally haploidized strains showed sensitivity to 6% lactic acid and low temperature at 13°C, respectively. The effect of the decreased copy number of the chromosomal terminal regions on ethanol production was analyzed. As compared with the host diploid strain, a 3.8% and 4.3% improvement in ethanol production in 10% glucose medium was observed for two strains in which one of two copies of the 197-kb left terminal region of chromosome V and one of two copies of the 195-kb left terminal region of chromosome X was deleted, respectively. These results indicate that artificial segmental haploidization might contribute to improvement of industrially important phenotypes and provide a new approach to breeding superior yeast strains. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Induction of diploid gynogenesis in an evolutionary model organism, the three-spined stickleback (Gasterosteus aculeatus

    Directory of Open Access Journals (Sweden)

    Scharsack Jörn P

    2011-09-01

    Full Text Available Abstract Background Rapid advances in genomics have provided nearly complete genome sequences for many different species. However, no matter how the sequencing technology has improved, natural genetic polymorphism complicates the production of high quality reference genomes. To address this problem, researchers have tried using artificial modes of genome manipulation such as gynogenesis for fast production of inbred lines. Results Here, we present the first successful induction of diploid gynogenesis in an evolutionary model system, the three-spined sticklebacks (Gasterosteus aculeatus, using a combination of UV-irradiation of the sperm and heat shock (HS of the resulting embryo to inhibit the second meiotic division. Optimal UV irradiation of the sperm was established by exposing stickleback sperm to a UV- light source at various times. Heat shock parameters like temperature, duration, and time of initiation were tested by subjecting eggs fertilized with UV inactivated sperm 5, 10, 15, 20, 25, or 30 minutes post fertilization (mpf to 30°C, 34°C, or 38°C for 2, 4, 6 or 8 minutes. Gynogen yield was highest when stickleback eggs were activated with 2 minutes UV-irradiated sperm and received HS 5 mpf at 34°C for 4 minutes. Conclusions Diploid gynogenesis has been successfully performed in three-spined stickleback. This has been confirmed by microsatellite DNA analysis which revealed exclusively maternal inheritance in all gynogenetic fry tested. Ploidy verification by flow cytometry showed that gynogenetic embryos/larvae exhibiting abnormalities were haploids and those that developed normally were diploids, i.e., double haploids that can be raised until adult size.

  18. Leydig cell damage after testicular irradiation for lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Shalet, S.M.; Horner, A.; Ahmed, S.R.; Morris-Jones, P.H.

    1985-01-01

    The effect of testicular irradiation on Leydig cell function has been studied in a group of boys irradiated between 1 and 5 years earlier for a testicular relapse of acute lymphoblastic leukemia. Six of the seven boys irradiated during prepubertal life had an absent testosterone response to HCG stimulation. Two of the four boys irradiated during puberty had an appropriate basal testosterone level, but the testosterone response to HCG stimulation was subnormal in three of the four. Abnormalities in gonadotropin secretion consistent with testicular damage were noted in nine of the 11 boys. Evidence of severe Leydig cell damage was present irrespective of whether the boys were studied within 1 year or between 3 and 5 years after irradiation, suggesting that recovery is unlikely. Androgen replacement therapy has been started in four boys and will be required by the majority of the remainder to undergo normal pubertal development.

  19. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Ottmann, Oliver G; Wassmann, Barbara

    2005-01-01

    Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukemia (ALL) includes at least one-quarter of all adults with ALL. Until recently, conventional chemotherapy programs that have been effective in other precursor B-cell ALL cases have been unable to cure patients with this diagnosis. Allogeneic stem cell transplantation early in first remission has been the recommended therapy. The availability of imatinib mesylate and other tyrosine kinase inhibitors and small molecules that affect the BCR/ABL signaling pathways may be changing the treatment paradigm and the prognosis for these patients. The results from clinical trials using imatinib in the frontline setting and in relapsed patients as well as preliminary experience treating imatinib-resistant Ph(+) ALL will be described.

  20. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    Directory of Open Access Journals (Sweden)

    Kayo Tokeji

    2016-01-01

    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.

  1. Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bongiovanni, Deborah; Saccomani, Valentina

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease caused by the malignant transformation of immature progenitors primed towards T-cell development. Clinically, T-ALL patients present with diffuse infiltration of the bone marrow by immature T-cell blasts high blood cell counts, mediastinal involvement, and diffusion to the central nervous system. In the past decade, the genomic landscape of T-ALL has been the target of intense research. The identification of specific genomic alterations has contributed to identify strong oncogenic drivers and signaling pathways regulating leukemia growth. Notwithstanding, T-ALL patients are still treated with high-dose multiagent chemotherapy, potentially exposing these patients to considerable acute and long-term side effects. This review summarizes recent advances in our understanding of the signaling pathways relevant for the pathogenesis of T-ALL and the opportunities offered for targeted therapy. PMID:28872614

  2. Acute lymphoblastic leukemia: a comprehensive review and 2017 update

    Science.gov (United States)

    Terwilliger, T; Abdul-Hay, M

    2017-01-01

    Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL. PMID:28665419

  3. Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

    Science.gov (United States)

    Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

    2015-01-01

    Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

  4. Primary orbital precursor T-cell lymphoblastic lymphoma

    DEFF Research Database (Denmark)

    Stenman, Lisa; Persson, Marta; Enlund, Fredrik

    2016-01-01

    Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical....... There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal...... genomic profile. The patient received chemotherapy according to the high-risk NOPHO protocol, followed by myeloablative allogenic bone marrow transplantation. At 35 months after diagnosis, the patient remained in complete first remission, but without light perception on his left eye. To the best of our...

  5. Evolution and maintenance of haploid-diploid life cycles in natural populations: The case of the marine brown alga Ectocarpus.

    Science.gov (United States)

    Couceiro, Lucía; Le Gac, Mickael; Hunsperger, Heather M; Mauger, Stéphane; Destombe, Christophe; Cock, J Mark; Ahmed, Sophia; Coelho, Susana M; Valero, Myriam; Peters, Akira F

    2015-07-01

    The evolutionary stability of haploid-diploid life cycles is still controversial. Mathematical models indicate that niche differences between ploidy phases may be a necessary condition for the evolution and maintenance of these life cycles. Nevertheless, experimental support for this prediction remains elusive. In the present work, we explored this hypothesis in natural populations of the brown alga Ectocarpus. Consistent with the life cycle described in culture, Ectocarpus crouaniorum in NW France and E. siliculosus in SW Italy exhibited an alternation between haploid gametophytes and diploid sporophytes. Our field data invalidated, however, the long-standing view of an isomorphic alternation of generations. Gametophytes and sporophytes displayed marked differences in size and, conforming to theoretical predictions, occupied different spatiotemporal niches. Gametophytes were found almost exclusively on the alga Scytosiphon lomentaria during spring whereas sporophytes were present year-round on abiotic substrata. Paradoxically, E. siliculosus in NW France exhibited similar habitat usage despite the absence of alternation of ploidy phases. Diploid sporophytes grew both epilithically and epiphytically, and this mainly asexual population gained the same ecological advantage postulated for haploid-diploid populations. Consequently, an ecological interpretation of the niche differences between haploid and diploid individuals does not seem to satisfactorily explain the evolution of the Ectocarpus life cycle. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  6. Evaluation of some Newly Developed Diploid Hybrids and their Breeding Value in 4x-2x Crosses

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The narrow genetic base in potato (Solanum tuberosum L. ) limits the progress in cultivar development.The rich diploid germplasm in the origin center of potato provide a unique resource for improvement of tetraploid potatoes. Seven newly developed diploid hybrids with 2n pollen production, all of which have S.phureja background,were developed and evaluated for their value in potato breeding. They were crossed as male parnets to six tetraploid Solanum tuberosum cultivars,and seeds in large quantity from eleven crosses were obtained. Main agronomic traits ,such as tuber yield ,tuber number,mean tuber weight ,tuber shape ,eye depth, skin smoothness, flesh color, and specific gravity, were measured for 4x-2x tetraploid progenies in seedling generation ,and their parents as well. All of the diploid hybrids had some merit for specific traits and the DH39 was more promising ;high specific gravity trait in some diploid hybrids was successfully introgressed into tetroploid progenies via 4x-2x crosses. These diploid hybrids have potential value in potato breeding.

  7. Treatment of Childhood Acute Lymphoblastic Leukemia Without Prophylactic Cranial Irradiation

    Science.gov (United States)

    Pui, Ching-Hon; Campana, Dario; Pei, Deqing; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Raimondi, Susana C.; Onciu, Mihaela; Coustan-Smith, Elaine; Kun, Larry E.; Jeha, Sima; Cheng, Cheng; Howard, Scott C.; Simmons, Vickey; Bayles, Amy; Metzger, Monika L.; Boyett, James M.; Leung, Wing; Handgretinger, Rupert; Downing, James R.; Evans, William E.; Relling, Mary V.

    2009-01-01

    Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia. PMID:19553647

  8. Outcome of children and adolescents with lymphoblastic lymphoma

    Directory of Open Access Journals (Sweden)

    Maria Christina Lopes Araújo Oliveira

    2015-10-01

    Full Text Available Summary Introduction: lymphoblastic lymphoma (LBL is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or younger with LBL admitted between January 1981 and December 2013. Patients were treated according to the therapy protocol used for acute lymphoblastic leucemia. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.6- 13.8. LBL had T-cell origin in 16 patients (59%. The most common primary manifestation in T-cell LBL was mediastinal involvement, in 9 patients (56%. Intra-abdominal tumor was the major site of involvement in patients with precursor B-LBL. Most patients had advanced disease (18 patients – 67% at diagnosis. Twenty-four patients (89% achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95, 22 patients (81% were alive in first complete remission. Five children (18.5% died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4. Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.

  9. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel.

    NARCIS (Netherlands)

    Oschlies, I.; Burkhardt, B.; Chassagne-Clement, C.; d'Amore, E.S.; Hansson, U.; Hebeda, K.M.; McCarthy, K.; Kodet, R.; Maldyk, J.; Mullauer, L.; Porwit, A.; Schmatz, A.I.; Tinguely, M.; Abramov, D.; Wotherspoon, A.; Zimmermann, M.; Reiter, A.; Klapper, W.

    2011-01-01

    The majority of lymphoblastic (precursor cell) neoplasms presents as leukemias. Consequently, the guidelines for lineage determination and subtyping of precursor cell neoplasms were primarily established for flow cytometry methods. Large-scale studies of nonleukemic lymphoblastic lymphomas are lacki

  10. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  11. UTX inhibition as selective epigenetic therapy against TAL1-driven T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Benyoucef, Aissa; Palii, Carmen G.; Wang, Chaochen; Porter, Christopher J.; Chu, Alphonse; Dai, Fengtao; Tremblay, Véronique; Rakopoulos, Patricia; Singh, Kulwant; Huang, Suming; Pflumio, Francoise; Hébert, Josée; Couture, Jean-Francois; Perkins, Theodore J.; Ge, Kai; Dilworth, F. Jeffrey; Brand, Marjorie

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures, and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes, leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage and activity of the histone 3 Lys27 (H3K27) demethylase UTX/KDM6A. Specifically, we identify UTX as a coactivator of TAL1 and show that it acts as a major regulator of the TAL1 leukemic gene expression program. Furthermore, we demonstrate that UTX, previously described as a tumor suppressor in T-ALL, is in fact a pro-oncogenic cofactor essential for leukemia maintenance in TAL1-positive (but not TAL1-negative) T-ALL. Exploiting this subtype-specific epigenetic vulnerability, we propose a novel therapeutic approach based on UTX inhibition through in vivo administration of an H3K27 demethylase inhibitor that efficiently kills TAL1-positive primary human leukemia. These findings provide the first opportunity to develop personalized epigenetic therapy for T-ALL patients. PMID:26944678

  12. TET2 promoter DNA methylation and expression analysis in pediatric B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ewa Musialik

    2014-03-01

    Full Text Available TET2 is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter was found in human cancer. Previous analysis revealed no TET2 mutations in acute lymphoblastic leukemia (ALL. Since the TET2 promoter methylation status in pediatric ALL has not been reported, the aim of the present study was to determine if promoter hypermethylation may be a mechanism of TET2 inactivation in a group of pediatric ALL cases. Methylation of TET2 promoter region in one (1/45 ALL B-common patient was detected by methylation specific polymerase chain reaction (PCR and subsequently analyzed by bisulfite sequencing. We found no correlation between promoter methylation and gene expression, measured by quantitative reverse transcriptase-PCR, however the level of TET2 expression in ALL group was significantly decreased compared to children’s normal peripheral blood mononuclear cells and isolated B-cells. TET2 promoter hypermethylation seems to have limited clinical relevance in childhood B-cell ALL due to its low frequency.

  13. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  14. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    Directory of Open Access Journals (Sweden)

    Ji Fuyun

    2011-10-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD, are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL patients as well as to take them as predictors for radiation toxicity. Methods Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively. Extracted DNA was analyzed by real-time PCR method. Results Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048. Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. Conclusions mtDNA and CD content may be considered as predictive factors to radiation toxicity.

  15. Diploid potato (Solanum tuberosum L.) as a model crop to study transgene expression.

    Science.gov (United States)

    Nadolska-Orczyk, Anna; Pietrusinska, Aleksandra; Binka-Wyrwa, Agnieszka; Kuc, Dominik; Orczyk, Wacław

    2007-01-01

    This paper presents a method of Agrobacterium-mediated transformation for two diploid breeding lines of potato, and gives a detailed analysis of reporter gene expression. In our lab, these lines were also used to obtain tetraploid somatic hybrids. We tested four newly prepared constructs based on the pGreen vector system containing the selection gene nptII or bar under the 35S or nos promoter. All these vectors carried gus under 35S. We also tested the pDM805 vector, with the bar and gus genes respectively under the Ubi1 and Act1 promoters, which are strong for monocots. The selection efficiency (about 17%) was highest in the stem and leaf explants after transformation with pGreen where nptII was under 35S. About half of the selected plants were confirmed via PCR and Southern blot analysis to be transgenic and, depending on the combination, 0 to 100% showed GUS expression. GUS expression was strongest in multi-copy transgenic plants where gus was under Act1. The same potato lines carrying multi-copy bar under Ubi1 were also highly resistant to the herbicide Basta. The suggestion of using Agrobacterium-mediated transformation of diploid lines of potato as a model crop is discussed herein.

  16. Chromosomal and morphological studies of diploid and polyploid cytotypes of Stevia rebaudiana (Bertoni Bertoni (Eupatorieae, Asteraceae

    Directory of Open Access Journals (Sweden)

    Vanessa M. de Oliveira

    2004-01-01

    Full Text Available In this study, we examined the chromosome number and some morphological features of strains of Stevia rebaudiana. The chromosomes were analyzed during mitosis and diakinesis, and the tetrad normality and pollen viability were also assessed. In addition, stomata and pollen were measured and some plant features were studied morphometrically. All of the strains had 2n = 22, except for two, which had 2n = 33 and 2n = 44. Pairing at diakinesis was n = 11II for all of the diploid strains, whereas the triploid and tetraploid strains had n = 11III and n = 11IV, respectively. Triploid and tetraploid plants had a lower tetrad normality rate than the diploids. All of the strains had inviable pollen. Thus, the higher the ploidy number, the greater the size of the pollen and the stomata, and the lower their number per unit area. The triploid strain produced the shortest plants and the lowest number of inflorescences, whereas the tetraploid strain had the largest leaves. Analysis of variance revealed highly significant differences among the strains, with a positive correlation between the level of ploidy and all of the morphological features examined.

  17. Toxic effects of glyphosate on diploid and triploid fin cell lines from Misgurnus anguillicaudatus.

    Science.gov (United States)

    Qin, Yanjie; Li, Xia; Xiang, Yang; Wu, Di; Bai, Liwen; Li, Zhuangzhuang; Liang, Yan

    2017-08-01

    We examined the toxic effects of glyphosate on diploid (DIMF) and triploid (TRMF) fin cell lines from the Oriental Weather Loach Misgurnus anguillicaudatus. The LC50 values of glyphosate estimated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay were 315.34 and 371.77 mg/L for DIMF and TRMF, respectively. Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities in DIMF and TRMF cells gradually increased and then decreased with increasing glyphosate concentrations, reaching a maximum at 240 mg/L glyphosate. In contrast, acetylcholinesterase (AChE) activities in DIMF and TRMF decreased with increasing concentrations of glyphosate in a concentration-dependent manner. SOD and AChE activities were generally significantly higher in TRMF compared with DIMF cells (P glyphosate compared with the control groups (P glyphosate. There were no differences in the rates of micronuclei and abnormal nuclei between DIMF and TRMF cells at any glyphosate concentration. Cell damage, including chromatin condensation, nucleus distortion, and broken and reduced endoplasmic reticulum, mitochondria, and ribosomes, were found in both cells treated with the LC50 concentration of glyphosate. Moreover, vacuolization and apoptotic bodies occurred in glyphosate-exposed DIMF and TRMF cells, indicating apoptosis. These results indicate that glyphosate in the range of tested concentrations represent a potential risk to loach through inhibiting proliferation of diploid and triploid cell lines and induces micronuclei and apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Profiling polyphenols of two diploid strawberry (Fragaria vesca) inbred lines using UHPLC-HRMS(n.).

    Science.gov (United States)

    Sun, Jianghao; Liu, Xianjin; Yang, Tianbao; Slovin, Janet; Chen, Pei

    2014-03-01

    Phenolic compounds in the fruits of two diploid strawberries (Fragaria vesca f. semperflorens) inbred lines-Ruegen F7-4 (a red-fruited genotype) and YW5AF7 (a yellow-fruited genotype) were characterised using ultra-high-performance liquid chromatography coupled with tandem high-resolution mass spectrometry (UHPLC-HRMS(n)). The changes of anthocyanin composition during fruit development and between Ruegen F7-4 and YW5AF7 were studied. About 67 phenolic compounds, including taxifolin 3-O-arabinoside, glycosides of quercetin, kaempferol, cyanidin, pelargonidin, peonidin, ellagic acid derivatives, and other flavonols were identified in these two inbred lines. Compared to the regular octoploid strawberry, unique phenolic compounds were found in F. vesca fruits, such as taxifolin 3-O-arabinoside (both) and peonidin 3-O-malonylglucoside (Ruegen F7-4). The results provide the basis for comparative analysis of polyphenolic compounds in yellow and red diploid strawberries, as well as with the cultivated octoploid strawberries.

  19. Flower and early fruit development in a diploid strawberry, Fragaria vesca.

    Science.gov (United States)

    Hollender, Courtney A; Geretz, Aviva C; Slovin, Janet P; Liu, Zhongchi

    2012-06-01

    The diploid woodland strawberry, Fragaria vesca, is being recognized as a model for the more complex octoploid commercial strawberry, Fragaria × ananassa. F. vesca exhibits a short seed to seed cycle, can be easily transformed by Agrobacteria, and a draft genome sequence has been published. These features, together with its similar flower structure, potentially make F. vesca a good model for studying the flower development of other members of the Rosaceae family, which contains many economically important fruit trees and ornamental plants. To propel F. vesca's role in genetic and genomic research and to facilitate the study of its reproductive development, we have investigated in detail F. vesca flower and early fruit development using a seventh generation inbred diploid line, Yellow Wonder 5AF7. We present here standardized developmental staging and detailed descriptions of morphological changes associated with flower and early fruit development based on images of hand dissected flowers, histological sections, and scanning electron microscopy. In situ hybridization with the F. vesca AGAMOUS homolog, FvAG, showed expression in young stamen and carpel primordia. This work lays the essential groundwork and standardization for future molecular, genetic, and genomic studies of F. vesca.

  20. Cytological, molecular mechanisms and temperature stress regulating production of diploid male gametes in Dianthus caryophyllus L.

    Science.gov (United States)

    Zhou, Xuhong; Mo, Xijun; Gui, Min; Wu, Xuewei; Jiang, Yalian; Ma, Lulin; Shi, Ziming; Luo, Ying; Tang, Wenru

    2015-12-01

    In plant evolution, because of its key role in sexual polyploidization or whole genome duplication events, diploid gamete formation is considered as an important component in diversification and speciation. Environmental stress often triggers unreduced gamete production. However, the molecular, cellular mechanisms and adverse temperature regulating diplogamete production in carnation remain poorly understood. Here, we investigate the cytological basis for 2n male gamete formation and describe the isolation and characterization of the first gene, DcPS1 (Dianthus Caryophyllus Parallel Spindle 1). In addition, we analyze influence of temperature stress on diploid gamete formation and transcript levels of DcPS1. Cytological evidence indicated that 2n male gamete formation is attributable to abnormal spindle orientation at male meiosis II. DcPS1 protein is conserved throughout the plant kingdom and carries domains suggestive of a regulatory function. DcPS1 expression analysis show DcPS1 gene probably have a role in 2n pollen formation. Unreduced pollen formation in various cultivation was sensitive to high or low temperature which was probably regulated by the level of DcPS1 transcripts. In a broader perspective, these findings can have potential applications in fundamental polyploidization research and plant breeding programs.

  1. Phylogeny and species delimitation of the C-genome diploid species in Oryza

    Institute of Scientific and Technical Information of China (English)

    Li-Li ZANG; Xin-Hui ZOU; Fu-Min ZHANG; Ziheng YANG; Song GE

    2011-01-01

    The diploid Oryza species with C-genome type possesses abundant genes useful for rice improvement and provides parental donors of many tetraploid species with the C-genome (BBCC,CCDD).Despite extensive studies,the phylogenetic relationship among the C-genome species and the taxonomic status of some taxa remain controversial.In this study,we reconstructed the phylogeny of three diploid species with C-genome (Oryza officinalis,O.rhizomatis,and O.eichingeri) based on sequences of 68 nuclear single-copy genes.We obtained a fully resolved phylogenetic tree,clearly indicating the sister relationship of O.officinalis and O.rhizomatis,with O.eichingeri being the more divergent lineage.Incongruent phylogenies of the C-genome species found in previous studies might result from lineage sorting,introgression/hybridization and limited number of genetic markers used.We further applied a recently developed Bayesian species delimitation method to investigate the species status of the Sri Lankan and African O.eichingeri.Analyses of two datasets (68 genes with a single sample,and 10 genes with multiple samples) support the distinct species status of the Sri Lankan and African O.eichingeri.In addition,we evaluated the impact of the number of sampled individuals and loci on species delimitation.Our simulation suggests that sampling multiple individuals is critically important for species delimitation,particularly for closely related species.

  2. Hybridization and reproductive isolation between diploid Erythronium mesochoreum and its tetraploid congener E. albidum (Liliaceae).

    Science.gov (United States)

    Roccaforte, Kathy; Russo, Sabrina E; Pilson, Diana

    2015-06-01

    Polyploidy has played an important role in angiosperm diversification, but how polyploidy contributes to reproductive isolation remains poorly understood. Most work has focused on postzygotic reproductive barriers, and the influence of ploidy differences on prezygotic barriers is understudied. To address these gaps, we quantified hybrid occurrence, interspecific self-compatibility differences, and the contributions of multiple pre- and postzygotic barriers to reproductive isolation between diploid Erythronium mesochoreum (Liliaceae) and its tetraploid congener Erythronium albidum. Reproductive isolation between the study species was nearly complete, and naturally occurring hybrids were infrequent and largely sterile. Although postzygotic barriers effected substantial reproductive isolation when considered in isolation, the study species' spatial distributions and pollinator assemblages overlapped little, such that interspecific pollen transfer is likely uncommon. We did not find evidence that E. albidum and E. mesochoreum differed in mating systems, indicating that self-incompatibility release may not have fostered speciation in this system. Ultimately, we demonstrate that E. albidum and E. mesochoreum are reproductively isolated by multiple, hierarchically-operating barriers, and we add to the currently limited number of studies demonstrating that early acting barriers such as pollinator-mediated isolation can be important for effecting and sustaining reproductive isolation in diploid-polyploid systems.

  3. A simple method for finding explicit analytic transition densities of diffusion processes with general diploid selection.

    Science.gov (United States)

    Song, Yun S; Steinrücken, Matthias

    2012-03-01

    The transition density function of the Wright-Fisher diffusion describes the evolution of population-wide allele frequencies over time. This function has important practical applications in population genetics, but finding an explicit formula under a general diploid selection model has remained a difficult open problem. In this article, we develop a new computational method to tackle this classic problem. Specifically, our method explicitly finds the eigenvalues and eigenfunctions of the diffusion generator associated with the Wright-Fisher diffusion with recurrent mutation and arbitrary diploid selection, thus allowing one to obtain an accurate spectral representation of the transition density function. Simplicity is one of the appealing features of our approach. Although our derivation involves somewhat advanced mathematical concepts, the resulting algorithm is quite simple and efficient, only involving standard linear algebra. Furthermore, unlike previous approaches based on perturbation, which is applicable only when the population-scaled selection coefficient is small, our method is nonperturbative and is valid for a broad range of parameter values. As a by-product of our work, we obtain the rate of convergence to the stationary distribution under mutation-selection balance.

  4. Genome downsizing and karyotype constancy in diploid and polyploid congeners: a model of genome size variation.

    Science.gov (United States)

    Poggio, Lidia; Realini, María Florencia; Fourastié, María Florencia; García, Ana María; González, Graciela Esther

    2014-06-26

    Evolutionary chromosome change involves significant variation in DNA amount in diploids and genome downsizing in polyploids. Genome size and karyotype parameters of Hippeastrum species with different ploidy level were analysed. In Hippeastrum, polyploid species show less DNA content per basic genome than diploid species. The rate of variation is lower at higher ploidy levels. All the species have a basic number x = 11 and bimodal karyotypes. The basic karyotypes consist of four short metacentric chromosomes and seven large chromosomes (submetacentric and subtelocentric). The bimodal karyotype is preserved maintaining the relative proportions of members of the haploid chromosome set, even in the presence of genome downsizing. The constancy of the karyotype is maintained because changes in DNA amount are proportional to the length of the whole-chromosome complement and vary independently in the long and short sets of chromosomes. This karyotype constancy in taxa of Hippeastrum with different genome size and ploidy level indicates that the distribution of extra DNA within the complement is not at random and suggests the presence of mechanisms selecting for constancy, or against changes, in karyotype morphology.

  5. Chromosomal instability in near-diploid colorectal cancer: a link between numbers and structure.

    Directory of Open Access Journals (Sweden)

    Martine Muleris

    Full Text Available Chromosomal instability (CIN plays a crucial role in tumor development and occurs mainly as the consequence of either missegregation of normal chromosomes (MSG or structural rearrangement (SR. However, little is known about the respective chromosomal targets of MSG and SR and the way these processes combined within tumors to generate CIN. To address these questions, we karyotyped a consecutive series of 96 near-diploid colorectal cancers (CRCs and distinguished chromosomal changes generated by either MSG or SR in tumor cells. Eighty-three tumors (86% presented with chromosomal abnormalities that contained both MSGs and SRs to varying degrees whereas all 13 others (14% showed normal karyotype. Using a maximum likelihood statistical method, chromosomes affected by MSG or SR and likely to represent changes that are selected for during tumor progression were found to be different and mostly mutually exclusive. MSGs and SRs were not randomly associated within tumors, delineating two major pathways of chromosome alterations that consisted of either chromosome gains by MSG or chromosomal losses by both MSG and SR. CRCs showing microsatellite instability (MSI presented with either normal karyotype or chromosome gains whereas MSS (microsatellite stable CRCs exhibited a combination of the two pathways. Taken together, these data provide new insights into the respective involvement of MSG and SR in near-diploid colorectal cancers, showing how these processes target distinct portions of the genome and result in specific patterns of chromosomal changes according to MSI status.

  6. Mutations affecting mitotic recombination frequency in haploids and diploids of the filamentous fungus Aspergillus nidulans.

    Science.gov (United States)

    Parag, Y; Parag, G

    1975-01-01

    A haploid strain of Asp. nidulans with a chromosome segment in duplicate (one in normal position on chromosome I, one translocated to chromosome II) shows mitotic recombination, mostly by conversion, in adE in a frequency slightly higher than in the equivalent diploid. A method has been devised, using this duplication, for the selection of rec and uvs mutations. Six rec mutations have been found which decrease recombination frequency in the haploid. One mutation selected as UV sensitive showed a hundred fold increase in recombination frequency in the haploid (pop mutation) and probably the same in diploids. The increased frequency is both in gene conversion and in crossing over, and the exchanges appear in clusters of two or more. pop is allelic to uvsB (Jansen, 1970) which had been found to affect mitotic but not meiotic recombination. It is suggested that mutations of this type interfere with the control mechanism which determines that high recombination is confirmed to the meiotic nuclei and avoided in somatic nuclei.

  7. Simple Sequence Repeat Genetic Linkage Maps of A-genome Diploid Cotton (Gossypium arboreum)

    Institute of Scientific and Technical Information of China (English)

    Xue-Xia Ma; Bao-Liang Zhou; Yan-Hui Lü; Wang-Zhen Guo; Tian-Zhen Zhang

    2008-01-01

    This study introduces the construction of the first intraspacific genetic linkage map of the A-genome diploid cotton with newly developed simple sequence repeat (SSR) markers using 189 F2 plants derived from the cross of two Asiatic parents were detected using 6 092 pairs of SSR primers. Two-hundred and sixty-eight pairs of SSR pdmers with better polymorphisms were picked out to analyze the F2 population. In total, 320 polymorphic bands were generated and used to construct a linkage map with JoinMap3.0. Two-hundred and sixty-seven loci, Including three phenotypic traits were mapped at a logarithms of odds ratio (LOD) ≥ 3.0 on 13 linkage groups. The total length of the map was 2 508.71 cM, and the average distance between adjacent markers was 9.40 cM. Chromosome assignments were according to the association of linkages with our backbone tetraploid specific map using the 89 similar SSR loci. Comparisons among the 13 suites of orthologous linkage groups revealed that the A-genome chromosomes are largely collinear with the At and Dt sub-genome chromosomes. Chromosomes associated with inversions suggested that allopolyploidization was accompanied by homologous chromosomal rearrangement. The inter-chromosomal duplicated loci supply molecular evidence that the A-genome diploid Asiatic cotton is paleopolyploid.

  8. Genetic relationships between diploid and allotetraploid cherry species (Prunus avium, Prunus x gondouinii and Prunus cerasus).

    Science.gov (United States)

    Tavaud, M; Zanetto, A; David, J L; Laigret, F; Dirlewanger, E

    2004-12-01

    Prunus avium L. (diploid, AA, 2n=2x=16), Prunus cerasus L. (allotetraploid, AAFF, 2n=4x=32) species, and their hybrid Prunus x gondouinii Rehd., constitute the most widely cultivated cherry tree species. P. cerasus is supposed to be an hybrid species produced by the union of unreduced P. avium gametes and normal P. fruticosa gametes. A continuum of morphological traits between these three species makes their assignation difficult. The aim of this paper is to study the genetic relationships between tetraploid and diploid cherry species. In all, 114 genotypes belonging to these species were analyzed using 75 AFLP markers. The coordinates of these genotypes on the first axis of a correspondence analysis allowed us to clearly distinguish each species, to identify misclassifications and to assign unknown genotypes to one species. We showed that there are specific alleles in P. cerasus, which are not present in the A genome of P. avium and which probably come from the F genome of P. cerasus. The frequencies of each marker in the A and the F genomes were estimated in order to identify A and F specific markers. We discuss the utility of these specific markers for finding the origin of the A and F genomes in the allopolyploid species.

  9. Comparative Proteomic Analysis of Mature Pollen in Triploid and Diploid Populus deltoides.

    Science.gov (United States)

    Zhang, Xiao-Ling; Zhang, Jin; Guo, Ying-Hua; Sun, Pei; Jia, Hui-Xia; Fan, Wei; Lu, Meng-Zhu; Hu, Jian-Jun

    2016-09-03

    Ploidy affects plant growth vigor and cell size, but the relative effects of pollen fertility and allergenicity between triploid and diploid have not been systematically examined. Here we performed comparative analyses of fertility, proteome, and abundances of putative allergenic proteins of pollen in triploid poplar 'ZhongHuai1' ('ZH1', triploid) and 'ZhongHuai2' ('ZH2', diploid) generated from the same parents. The mature pollen was sterile in triploid poplar 'ZH1'. By applying two-dimensional gel electrophoresis (2-DE), a total of 72 differentially expressed protein spots (DEPs) were detected in triploid poplar pollen. Among them, 24 upregulated and 43 downregulated proteins were identified in triploid poplar pollen using matrix-assisted laser desorption/ionisation coupled with time of-flight tandem mass spectrometer analysis (MALDI-TOF/TOF MS/MS). The main functions of these DEPs were related with "S-adenosylmethionine metabolism", "actin cytoskeleton organization", or "translational elongation". The infertility of triploid poplar pollen might be related to its abnormal cytoskeletal system. In addition, the abundances of previously identified 28 putative allergenic proteins were compared among three poplar varieties ('ZH1', 'ZH2', and '2KEN8'). Most putative allergenic proteins were downregulated in triploid poplar pollen. This work provides an insight into understanding the protein regulation mechanism of pollen infertility and low allergenicity in triploid poplar, and gives a clue to improving poplar polyploidy breeding and decreasing the pollen allergenicity.

  10. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Cells in Vitro

    Science.gov (United States)

    1982-09-07

    Chsaactariaane a/lthe Transformed C4110. essential amino acids. IX euenstial amino acida.,USAq 2.0 mM giutamine, IX vitamina , 0.2% sodium Taumor omnk in...subcutaneous injection of *&mino acids. 2.0 mM glusamine. IX vitamina , SX 10’ carcinogen-treazed or control cells ssa. 0.2% sodium bicarbonate. S iAg/ml

  11. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Fibroblasts in vitro.

    Science.gov (United States)

    1985-06-12

    coumarin; QU, quercetin; ISO, isoquinoline; I-Me-NA, l-methylnicotinamide; HMBA, hexamethylene bisacetamide; CAFF, caffeine; PRIM, primycin . The cell...of these anti- cells after PD2o biotics (nos 4,5) and of the antibiotic primycin I PD1 0.7AM MNNG alone 185 t 18 (2)a " (no.13) occurs at much lower...Pharmaceuticals 38, 168-181. % (Piscataway, NJ) and Primycin from Chinoin Ltd [121 Amery, W.K. and Butterworth, B.S. (1983) Int. J. (Budapest) through the

  12. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Fibroblasts in vitro.

    Science.gov (United States)

    1983-12-29

    determined as " .%. a measure of the growth phase (Cristofalo aid Sharf , 1973). The cultures were maintained in complete growth medium com- posed of... Sharf , 1973) dropped to ɘ.1%. At point R . [. (Fig. 1), the 0M medium was replaced with CM (Milo et al., ... .[-:1981), and IN was added to the CM. After...1982). Ann. N.Y. Acad. Sci. 207, 19-27. Cristofalo, V., and Sharf , B. (1973). Exp. Cell Res. 76, 419-427. Dedman, F. R., Welsh, M. J., and Means, A

  13. Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia

    Science.gov (United States)

    Brissot, Eolia; Labopin, Myriam; Beckers, Marielle M.; Socié, Gérard; Rambaldi, Alessandro; Volin, Liisa; Finke, Jürgen; Lenhoff, Stig; Kröger, Nicolaus; Ossenkoppele, Gert J.; Craddock, Charles F.; Yakoub-Agha, Ibrahim; Gürman, Günhan; Russell, Nigel H.; Aljurf, Mahmoud; Potter, Michael N.; Nagler, Armon; Ottmann, Oliver; Cornelissen, Jan J.; Esteve, Jordi; Mohty, Mohamad

    2015-01-01

    This study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long-term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute Leukemia Working Party included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using a human leukocyte antigen-identical sibling or human leukocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred and ninety patients received tyrosine kinase inhibitors before transplant, 329 at induction and 274 at consolidation. Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at five years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P=0.04) and was associated with lower relapse incidence (HR=0.5; P=0.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitor administration to be a significant factor for improved leukemia-free survival (HR=0.44; P=0.002) and overall survival (HR=0.42; P=0.004), and a lower relapse incidence (HR=0.40; P=0.01). Over the past decade, administration of tyrosine kinase inhibitors before allogeneic stem cell transplantation has significantly improved the long-term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine kinase inhibitors in the post-transplant setting. PMID:25527562

  14. Unrelated umbilical cord blood transplant for adult acute lymphoblastic leukemia in first and second complete remission: a comparison with allografts from adult unrelated donors

    Science.gov (United States)

    Marks, David I.; Woo, Kwang Ahn; Zhong, Xiaobo; Appelbaum, Frederick R.; Bachanova, Veronika; Barker, Juliet N.; Brunstein, Claudio G.; Gibson, John; Kebriaei, Partow; Lazarus, Hillard M.; Olsson, Richard; Perales, Miguel-Angel; Pidala, Joseph; Savani, Bipin; Rocha, Vanderson; Eapen, Mary

    2014-01-01

    Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and –DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2–4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor. PMID:24056817

  15. Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias.

    Science.gov (United States)

    Fei, Fei; Stoddart, Sonia; Groffen, John; Heisterkamp, Nora

    2010-05-01

    The emergence of resistance to tyrosine kinase inhibitors due to point mutations in Bcr/Abl is a challenging problem for Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) patients, especially for those with the T315I mutation, against which neither nilotinib or dasatinib shows significant activity. VX-680 is a pan-Aurora kinase inhibitor active against all Bcr/Abl proteins but has not been extensively examined in preclinical models of Ph-positive ALL. Here, we have tested VX-680 for the treatment of Bcr/Abl-positive ALL when leukemic cells are protected by the presence of stroma. Under these conditions, VX-680 showed significant effects on primary human Ph-positive ALL cells both with and without the T315I mutation, including ablation of tyrosine phosphorylation downstream of Bcr/Abl, decreased viability, and induction of apoptosis. However, drug treatment of human Ph-positive ALL cells for 3 days followed by drug removal allowed the outgrowth of abnormal cells 21 days later, and on culture of mouse Bcr/Abl ALL cells on stroma with lower concentrations of VX-680, drug-resistant cells emerged. Combined treatment of human ALL cells lacking the T315I mutation with both VX-680 and dasatinib caused significantly more cytotoxicity than each drug alone. We suggest that use of VX-680 together with a second effective drug as first-line treatment for Ph-positive ALL is likely to be safer and more useful than second-line treatment with VX-680 as monotherapy for drug-resistant T315I Ph-positive ALL.

  16. Targeted Resequencing of 9p in Acute Lymphoblastic Leukemia Yields Concordant Results with Array CGH and Reveals Novel Genomic Alterations

    NARCIS (Netherlands)

    Sarhadi, V.K.; Lahti, L.M.; Scheinin, I.; Tyybäkinoja, A.; Savola, S.; Usvasalo, A.; Räty, R.; Elonen, E.; Saarinen-Pihkala, U.M.; Knuutila, S.

    2013-01-01

    Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparis

  17. The use of optical microscope equipped with multispectral detector to distinguish different types of acute lymphoblastic leukemia

    Science.gov (United States)

    Pronichev, A. N.; Polyakov, E. V.; Tupitsyn, N. N.; Frenkel, M. A.; Mozhenkova, A. V.

    2017-01-01

    The article describes the use of a computer optical microscopy with multispectral camera to characterize the texture of blasts bone marrow of patients with different variants of acute lymphoblastic leukemia: B- and T- types. Specific characteristics of the chromatin of the nuclei of blasts for different types of acute lymphoblastic leukemia were obtained.

  18. Time trends in the incidence of acute lymphoblastic leukemia among children 1976-2002: a population-based Nordic study

    DEFF Research Database (Denmark)

    Svendsen, Anne Louise; Feychting, Maria; Klaeboe, Lars

    2007-01-01

    We studied the incidence of childhood acute lymphoblastic leukemia in Denmark, Finland, Norway, and Sweden during 1976-2002, on the basis of data from national cancer registries. The incidence of acute lymphoblastic leukemia increased with the calendar period until 1983, and with the birth cohort...

  19. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

  20. Diploid oocyte formation and tetraploid embryo development induced by cytochalasin B in bovine.

    Science.gov (United States)

    Bai, Chunling; Liu, Hui; Liu, Ying; Wu, Xia; Cheng, Lei; Bou, Shorgan; Li, Guang-Peng

    2011-02-01

    Tetraploid embryos are a useful model for postimplantation development of polyploidy cells, and tetraploid cells are an advantage in studies for chimeras yielding offspring completely derived from embryo stem cells or induced pluripotent cells. This study was designed to investigate the effects of cytochalasin B (CB) on bovine oocyte meiosis, and to induce the formation of diploid oocytes and tetraploid embryos. The results showed that: (1) incubation of oocytes in CB at ≥2.0 μg/mL concentrations for 24 h significantly decreased oocyte maturation and the matured oocytes' haploid composition. Over 50% of the CB-treated oocytes did not expel PB1 (non-PB1), and most of the non-PB1 oocytes contained 2n (60) chromosomes. (2) Pretreatment of oocytes with CB at concentrations of 7.5 and 15 μg/mL for 10 h significantly decreased oocyte maturation. Posttreatment of oocytes with CB resulted in most of the oocytes containing 2n chromosomes. (3) The parthenogenetic blastocysts (25-28%) derived from the non-PB1 oocytes of posttreatment group was significantly higher than that from pretreatment, whole period treatment, and the control oocytes (12-16%). (4) Cytogenetic analysis of the embryos derived from CB-treated non-PB1 oocytes resulted in 74% of the one-cell stage embryos being 4n = 120 chromosomes, 82% of two-cell stage embryos contained 4n chromosomes in each blastomere, and 75% of the blastocysts were tetraploidy (4n = 120). (6) The stopped uncleaved one-cell embryos showed an amazing phenomenon of over 15% of them containing extra chromosomes, which suggested multiple DNA duplication occurred within 40 h after activation. In conclusion, CB inhibits PB1 extrusion, disfigures spindle structure, decreases oocyte maturation, and results in formation of diploid (2n or 4c) oocytes. The diploid oocytes resulted in a higher development of tetraploid embryos, which would be a unique approach for the production of tetraploid embryos in bovine.

  1. REARRANGEMENT IN THE B-GENOME FROM DIPLOID PROGENITOR TO WHEAT ALLOPOLYPOLID

    Directory of Open Access Journals (Sweden)

    Salina E.A.

    2012-08-01

    Full Text Available Three key periods that were accompanied by considerable rearrangements in the B genome of wheat and its progenitor can be considered. The first period covers the period from the divergence of diploid Triticum and Aegilops species from their common progenitor (2.5–6 million years ago to formation of the tetraploid T. diccocoides (about 500 thousand years ago. Significant genomic rearrangements in the diploid progenitor of the B genome, Ae. speltoides (SS genome, involved a considerable amplification of repeated DNA sequences, which led to an increase in the number of heterochromatin blocks on chromosomes relative to other diploid Aegilops and Triticum species. Our analysis has demonstrated that during this period the Spelt1 repeats intensively amplified as well as several mobile elements proliferated, in particular, the genome-specific gypsy LTR-retrotransposon Fatima and CACTA DNA-transposon Caspar. The second period in the B-genome evolution was associated with the emergence of tetraploid (BBAA genome and its subsequent evolution. The third most important event leading to the next rearrangement of the B genome took place relatively recently, 7000–9500 years ago, being associated with the emergence of hexaploid wheat with the genomic formula BBAADD. The evolution of the B/S genome involved intergenomic and intragenomic translocations and chromosome inversions. So far, five rearrangements in the B-genome chromosomes of polyploid wheats has been observed and described; the majority of them took place during the formation and evolution of tetraploid species. The mapping of the S-genome chromosomes and comparison with the B-genome chromosome maps have demonstrated that individual rearrangements pre-existed in Ae. speltoides; moreover, Ae. speltoides is polymorphic for these rearrangements.Chromosome 5B is nearly 870 Mbp (5BL = 580 Mbp and 5BS = 290 Mbp and is known to carry important genes controlling the key aspects of wheat biology, in

  2. Water and Nutrient Use Efficiency in Diploid, Tetraploid and Hexaploid Wheats

    Institute of Scientific and Technical Information of China (English)

    Ming-Li Huang; Xi-Ping Deng; Yu-Zong Zhao; Sheng-Lu Zhou; Shinobu Inanaga; Satoshi Yamada; Kiyoshi Tanaka

    2007-01-01

    Three diploid (Triticum boeoticum, AA; Aegilops speltoides, BB and Ae. tauschii, DD), two tetraplold (T. dlcoccoides,AABB and T. dicoccon, AABB) and one hexaploid (T. vulgare, AABBDD) varieties of wheat, which are very important in the evolution of wheat were chosen in this study. A pot experiment was carried out on the wheat under different water and nutrient conditions (i) to understand the differences in biomass, yield, water use efficiency (WUE), and nutrient (N, P and K) use efficiency (uptake and utilization efficiency) among ploldles in the evolution of wheat; (ii) to clarify the effect of water and nutrient conditions on water and nutrient use efficiency; and (iii) to assess the relationship of water and nutrient use efficiency in the evolution of wheat. Our results showed that from diploid to tetraploid then to hexaploid during the evolution of wheat, both root biomass and above-ground biomass increased initially and then decreased. Water consumption for transpiration decreased remarkably, correlating with the decline of the growth period, while grain yield, harvest index, WUE, N, P and K uptake efficiency, and N, P and K utilization efficiency increased significantly. Grain yield, harvest index and WUE decreased in the same order: T.vulgare > T. dicoccon > T. dicoccoides > Ae. tauschii > Ae. speltoides > T. boeoticum. Water stress significantly decreased root biomass, above-ground biomass, yield, and water consumption for transpiration by 47-52%, butremarkably increased WUE. Increasing the nutrient supply increased wheat above-ground biomass, grain yield,harvest index, water consumption for transpiration and WUE under different water levels, but reduced root biomass under drought conditions. Generally, water stress and low nutrient supply resulted in the lower nutrientuptake efficiency of wheat. However, water and nutrient application had no significant effects on nutrient utilization efficiency, suggesting that wheat nutrient utilization

  3. Breakpoint sites disclose the role of the V(D)J recombination machinery in the formation of T-cell receptor (TCR) and non-TCR associated aberrations in T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Larmonie, Nicole S D; Dik, Willem A; Meijerink, Jules P P; Homminga, Irene; van Dongen, Jacques J M; Langerak, Anton W

    2013-08-01

    Aberrant recombination between T-cell receptor genes and oncogenes gives rise to chromosomal translocations that are genetic hallmarks in several subsets of human T-cell acute lymphoblastic leukemias. The V(D)J recombination machinery has been shown to play a role in the formation of these T-cell receptor translocations. Other, non-T-cell receptor chromosomal aberrations, such as SIL-TAL1 deletions, have likewise been recognized as V(D)J recombination associated aberrations. Despite the postulated role of V(D)J recombination, the extent of the V(D)J recombination machinery involvement in the formation of T-cell receptor and non-T-cell receptor aberrations in T-cell acute lymphoblastic leukemia is still poorly understood. We performed a comprehensive in silico and ex vivo evaluation of 117 breakpoint sites from 22 different T-cell receptor translocation partners as well as 118 breakpoint sites from non-T-cell receptor chromosomal aberrations. Based on this extensive set of breakpoint data, we provide a comprehensive overview of T-cell receptor and oncogene involvement in T-ALL. Moreover, we assessed the role of the V(D)J recombination machinery in the formation of chromosomal aberrations, and propose an up-dated mechanistic classification on how the V(D)J recombination machinery contributes to the formation of T-cell receptor and non-T-cell receptor aberrations in human T-cell acute lymphoblastic leukemia.

  4. The comparative reproductive biology of a tetraploid species, Hedychium villosum, and its diploid progenitor H. tenuiflorum (Zingiberaceae).

    Science.gov (United States)

    Gao, J Y; Liu, Q; Li, Q J

    2014-05-01

    The evolutionary advantages of polyploidy may result from a number of changes in floral traits and breeding system, which may enable polyploids to exploit new habitats and become widespread. In this study, we comparatively investigated the floral biology of the tetraploid species Hedychium villosum and its diploid progenitor H. tenuiflorum, to assess reproductive divergence between the two species. The results showed that flowers of the tetraploid species last longer and produce more nectar than did diploid species. The flowering times of the two species did not overlap at all. Observations of floral visitors in natural populations demonstrated that butterflies and hawkmoths were effective pollinators of both species, but there was a significant difference in butterfly and hawkmoth assemblages between the two species. The hand-pollination experiments and pollen tube growth experiments suggested that diploid H. tenuiflorum was self-incompatible, while tetraploid H. villosum was completely self-compatible. H. villosum has a much wider distribution range and occupies more diverse habitats than H. tenuiflorum. Polyploidisation may enable tetraploid H. villosum to exploit new habitats previously unavailable to diploid H. tenuiflorum.

  5. Hybrid origins and the earliest stages of diploidization in the highly successful recent polyploid Capsella bursa-pastoris.

    Science.gov (United States)

    Douglas, Gavin M; Gos, Gesseca; Steige, Kim A; Salcedo, Adriana; Holm, Karl; Josephs, Emily B; Arunkumar, Ramesh; Ågren, J Arvid; Hazzouri, Khaled M; Wang, Wei; Platts, Adrian E; Williamson, Robert J; Neuffer, Barbara; Lascoux, Martin; Slotte, Tanja; Wright, Stephen I

    2015-03-03

    Whole-genome duplication (WGD) events have occurred repeatedly during flowering plant evolution, and there is growing evidence for predictable patterns of gene retention and loss following polyploidization. Despite these important insights, the rate and processes governing the earliest stages of diploidization remain poorly understood, and the relative importance of genetic drift, positive selection, and relaxed purifying selection in the process of gene degeneration and loss is unclear. Here, we conduct whole-genome resequencing in Capsella bursa-pastoris, a recently formed tetraploid with one of the most widespread species distributions of any angiosperm. Whole-genome data provide strong support for recent hybrid origins of the tetraploid species within the past 100,000-300,000 y from two diploid progenitors in the Capsella genus. Major-effect inactivating mutations are frequent, but many were inherited from the parental species and show no evidence of being fixed by positive selection. Despite a lack of large-scale gene loss, we observe a decrease in the efficacy of natural selection genome-wide due to the combined effects of demography, selfing, and genome redundancy from WGD. Our results suggest that the earliest stages of diploidization are associated with quantitative genome-wide decreases in the strength and efficacy of selection rather than rapid gene loss, and that nonfunctionalization can receive a "head start" through a legacy of deleterious variants and differential expression originating in parental diploid populations.

  6. Two major groups of chloroplast DNA haplotypes in diploid and tetraploid Aconitum subgen. Aconitum (Ranunculaceae in the Carpathians

    Directory of Open Access Journals (Sweden)

    J. Mitka

    2016-04-01

    Full Text Available Aconitum in Europe is represented by ca. 10% of the total number of species and the Carpathian Mts. are the center of the genus variability in the subcontinent. We studied the chloroplast DNA intergenic spacer trnL(UAG-rpl32- ndhF (cpDNA variability of the Aconitum subgen. Aconitum in the Carpathians: diploids (2n=16, sect. Cammarum, tetraploids (2n=32, sect. Aconitum and triploids (2n=24, nothosect. Acomarum. Altogether 25 Aconitum accessions representing the whole taxonomic variability of the subgenus were sequenced and subjected to phylogenetic analyses. Both parsimony, Bayesian and character network analyses showed the two distinct types of the cpDNA chloroplast, one typical of the diploid and the second of the tetraploid groups. Some specimens had identical cpDNA sequences (haplotypes and scattered across the whole mountain arch. In the sect. Aconitum 9 specimens shared one haplotype, while in the sect. Camarum one haplotype represents 4 accessions and the second – 5 accessions. The diploids and tetraploids were diverged by 6 mutations, while the intrasectional variability amounted maximally to 3 polymorphisms. Taking into consideration different types of cpDNA haplotypes and ecological profiles of the sections (tetraploids – high‑mountain species, diploids – species from forest montane belt we speculate on the different and independent history of the sections in the Carpathians.

  7. Diploidized eggs reprogram adult somatic cell nuclei to pluripotency in nuclear transfer in medaka fish (Oryzias latipes).

    Science.gov (United States)

    Bubenshchikova, Ekaterina; Kaftanovskaya, Elena; Motosugi, Nami; Fujimoto, Takafumi; Arai, Katsutoshi; Kinoshita, Masato; Hashimoto, Hisashi; Ozato, Kenjiro; Wakamatsu, Yuko

    2007-12-01

    Reprogramming of adult somatic cell nuclei to pluripotency has been unsuccessful in non-mammalian animals, primarily because of chromosomal aberrations in nuclear transplants, which are considered to be caused by asynchrony between the cell cycles of the recipient egg and donor nucleus. In order to normalize the chromosomal status, we used diploidized eggs by retention of second polar body release, instead of enucleated eggs, as recipients in nuclear transfer of primary culture cells from the caudal fin of adult green fluorescent protein gene (GFP) transgenic medaka fish (Oryzias latipes). We found that 2.7% of the reconstructed embryos grew into adults that expressed GFP in various tissues in the same pattern as in the donor fish. Moreover, these fish were diploid, fertile and capable of passing the marker gene to the next generation in Mendelian fashion. We hesitate to call these fish 'clones' because we used non-enucleated eggs as recipients; in effect, they may be chimeras consisting of cells derived from diploid recipient nuclei and donor nuclei. In either case, fish adult somatic cell nuclei were reprogrammed to pluripotency and differentiated into a variety of cell types including germ cells via the use of diploidized recipient eggs.

  8. Diploid males support a two-step mechanism of endosymbiont-induced thelytoky in a parasitoid wasp

    NARCIS (Netherlands)

    Ma, W.J.; Pannebakker, B.A.; Zande, van de L.; Schwander, T.; Wertheim, B.; Beukeboom, L.W.

    2015-01-01

    Background Haplodiploidy, where females develop from diploid, fertilized eggs and males from haploid, unfertilized eggs, is abundant in some insect lineages. Some species in these lineages reproduce by thelytoky that is caused by infection with endosymbionts: infected females lay haploid eggs that u

  9. The contribution of haploids, diploids and clones to fine-scale population structure in the seaweed Cladophoropsis membranacea (Chlorophyta)

    NARCIS (Netherlands)

    van der Strate, H. J.; van de Zande, L.; Stam, W.T.; Olsen, J.L.

    2002-01-01

    Local populations of Cladophoropsis membranacea exist as mats of coalesced thalli composed of free-living haploid and diploid plants including clonally reproduced plants of either phase. None of the phases are morphologically distinguishable. We used eight microsatellite loci to explore clonality an

  10. The culturable intestinal microbiota of triploid and diploid juvenile Atlantic salmon (Salmo salar - a comparison of composition and drug resistance

    Directory of Open Access Journals (Sweden)

    Cantas Leon

    2011-11-01

    Full Text Available Abstract Background With the increased use of ploidy manipulation in aquaculture and fisheries management this investigation aimed to determine whether triploidy influences culturable intestinal microbiota composition and bacterial drug resistance in Atlantic salmon (Salmo salar. The results could provide answers to some of the physiological differences observed between triploid and diploid fish, especially in terms of fish health. Results No ploidy effect was observed in the bacterial species isolated, however, triploids were found to contain a significant increase in total gut microbiota levels, with increases in Pseudomonas spp., Pectobacterium carotovorum, Psychrobacter spp., Bacillus spp., and Vibrio spp., (12, 42, 9, 10, and 11% more bacteria in triploids than diploids, respectively, whereas a decrease in Carnobacterium spp., within triploids compared to diploids was close to significant (8% more bacteria in diploids. With the exception of gentamicin, where no bacterial resistance was observed, bacterial isolates originating from triploid hosts displayed increased resistance to antibacterials, three of which were significant (tetracycline, trimethoprim, and sulphonamide. Conclusion Results indicate that triploidy influences both the community and drug resistance of culturable intestinal microbiota in juvenile salmon. These results demonstrate differences that are likely to contribute to the health of triploid fish and have important ramifications on the use of antibacterial drugs within aquaculture.

  11. Development and evaluation of a genome-wide 6K SNP array for diploid sweet cherry and tetraploid sour cherry

    Science.gov (United States)

    High-throughput genome scans are important tools for genetic studies and breeding applications. Here, a 6K SNP array for use with the Illumina Infinium® system was developed for diploid sweet cherry (Prunus avium) and allotetraploid sour cherry (P. cerasus). This effort was led by RosBREED, a commun...

  12. Mutations in AtPS1 (Arabidopsis thaliana parallel spindle 1 lead to the production of diploid pollen grains.

    Directory of Open Access Journals (Sweden)

    Isabelle d'Erfurth

    2008-11-01

    Full Text Available Polyploidy has had a considerable impact on the evolution of many eukaryotes, especially angiosperms. Indeed, most--if not all-angiosperms have experienced at least one round of polyploidy during the course of their evolution, and many important crop plants are current polyploids. The occurrence of 2n gametes (diplogametes in diploid populations is widely recognised as the major source of polyploid formation. However, limited information is available on the genetic control of diplogamete production. Here, we describe the isolation and characterisation of the first gene, AtPS1 (Arabidopsis thaliana Parallel Spindle 1, implicated in the formation of a high frequency of diplogametes in plants. Atps1 mutants produce diploid male spores, diploid pollen grains, and spontaneous triploid plants in the next generation. Female meiosis is not affected in the mutant. We demonstrated that abnormal spindle orientation at male meiosis II leads to diplogamete formation. Most of the parent's heterozygosity is therefore conserved in the Atps1 diploid gametes, which is a key issue for plant breeding. The AtPS1 protein is conserved throughout the plant kingdom and carries domains suggestive of a regulatory function. The isolation of a gene involved in diplogamete production opens the way for new strategies in plant breeding programmes and progress in evolutionary studies.

  13. A microsatellite-based method for genotyping diploid and triploid water frogs of the Rana esculenta hybrid complex

    DEFF Research Database (Denmark)

    Christiansen, Ditte Guldager

    2005-01-01

    Rana esculenta is a hybrid between Rana lessonae (LL) and Rana ridibunda (RR), and hybrids may be diploid (LR) or triploid (LLR or LRR). Genotypes can be roughly determined from erythrocyte size and morphometry in adult frogs, but accurate genotyping requires more labourious methods. Here I...

  14. A molecular marker-based linkage map of diploid bananas (Musa acuminata).

    Science.gov (United States)

    Fauré, S; Noyer, J L; Horry, J P; Bakry, F; Lanaud, C; Gońzalez de León, D

    1993-12-01

    A partial molecular linkage map of the Musa acuminata diploid genome is presented. This map is based on 58 RFLP, four isozyme and 28 RAPD markers segregating in an F2 population of 92 individuals. A total of 90 loci was detected, 77 of which were placed on 15 linkage groups while 13 segregated independently. Segregation distortions were shown by 36% of all loci, mostly favoring the male parent. Chromosome structural rearrangements were believed to be one of the main causes of these distortions. The use of genetic linkage data to further the genetic and evolutionary knowledge of the genus Musa, as well as to help improve the design of breeding strategies, is discussed.

  15. Primary studies on tissue culture from mature embryos in diploid and tetraploid wheat

    Institute of Scientific and Technical Information of China (English)

    Ruiming BI; Honggang WANG

    2008-01-01

    Using mature embryos (MEs) as the explants,the callus induction,embryogenic callus differentiation,plantlet regeneration and culture efficiency in diploid and tetraploid wheat of four genotypes were studied.The tested four genotypes wheat included cultivable emmer wheat ( Triticum dicoccum Schuble),durum wheat ( Triticum durum Desf.) and the common wheat progenitors Triticum dicoccoides and Triticum aegilopides.Results indicated that there were significant differences in the efficiency of callus induction,callus differentiation and plant regeneration among the tested genotypes.The efficiency of differentiation and regeneration shows strong genotype dependence.The rates of callus induction,embryogenic callus differentiation,plantlet regeneration and culture efficiency respectively were 95.00%,90.00%,32.40%,and 27.70% in cultivable emmer wheat,which were significantly higher than other tested genotypes.Therefore,this study has provided a basis for genetic transformation,gene cloning and molecular plant breeding in wheat and other related species.

  16. Repeated batch fermentation from raw starch using a maltose transporter and amylase expressing diploid yeast strain.

    Science.gov (United States)

    Yamakawa, Syun-ichi; Yamada, Ryosuke; Tanaka, Tsutomu; Ogino, Chiaki; Kondo, Akihiko

    2010-06-01

    We successfully demonstrated batch ethanol fermentation repeated ten times from raw starch with high ethanol productivity. We constructed a yeast diploid strain coexpressing the maltose transporter AGT1, alpha-amylase, and glucoamylase. The introduction of AGT1 allows maltose and maltotriose fermentation as well as the improvement of amylase activities. We also found that alpha-amylase activity during fermentation was retained by the addition of 10 mM calcium ion and that the highest alpha-amylase activity was 9.26 U/ml during repeated fermentation. The highest ethanol productivity was 2.22 g/l/h at the fourth batch, and after ten cycles, ethanol productivity of more than 1.43 g/l/h was retained, as was alpha-amylase activity at 6.43 U/ml.

  17. Estimation of Genetic Effect for 2N Pollen Producing Diploid Hybrids

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Three 2x clones with 2n pollen production, BPH32-2,BPH32-5 and W5295,7, were each mated with three 4x cultivars, Raritan, Superior and Trent, in an incomplete diallel cross design. Estimates of various heritability for tuber yield per plant are that h2m is 37.20%,h2f 16.30%,h2mf 23.30%,h2B 76.70% and h2N 53.40%. Estimates of general combining ability(GCA) and specific combining ability(SCA) are 69.60% and 30.30%,respectively. The results suggest that additive effect of genes for tuber yield is obvious. The 2n pollen producing diploid hybrids have good breeding values for yield ,earliness and starch content.

  18. Radiation-induced hypopituitarism in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mehrdad Mirouliaei

    2013-01-01

    Full Text Available Background: Acute Lymphoblastic Leukemia (ALL is the most common malignancy among children for whom radiotherapy and chemotherapy are used for treatment. When hypothalamus-pituitary axis is exposed to radiotherapy, children′s hormone level and quality of life are influenced. The aim of this study is to determine late effects of radiotherapy on hormonal level in these patients. Materials and Methods: In this study 27 children with ALL, who have been referred to Shahid Ramezanzadeh Radiation Oncology Center in Yazd-Iran and received 18-24 Gy whole brain radiation with Cobalt 60 or 9 MV linear accelerator, were assessed. These patient′s basic weight, height and hormonal levels were measured before radiotherapy and also after different periods of time. Results: GHD (growth hormone deficiency after clonidine stimulation test was observed in 44% ( n=12 and that in 50% of them ( n=6, less than 1 year, had been passed from their radiation therapy. None of these patients demonstrated hormone deficiency in other axes. Conclusions: This study showed that even application of a 18-24 Gy radiation dose might influence growth hormone levels; therefore, we recommend reduction of radiotherapy dose in such patients whenever possible.

  19. ETV6-RUNX1 (+) Acute Lymphoblastic Leukaemia in Identical Twins.

    Science.gov (United States)

    Ford, Anthony M; Greaves, Mel

    2017-01-01

    Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1).The natural history of childhood ALL is almost entirely clinically silent and is well advanced at the point of diagnosis. It has, however, been possible to backtrack this process through molecular analysis of appropriate clinical samples: (i) leukaemic clones in monozygotic twins that are either concordant or discordant for ALL; (ii) archived neonatal blood spots or Guthrie cards from individuals who later developed leukaemia; and (iii) stored, viable cord blood cells.Here, we outline our studies on the aetiology and pathology of childhood ALL that provide molecular evidence for a monoclonal, prenatal origin of ETV6-RUNX1+ leukaemia in monozygotic identical twins. We provide mechanistic support for the concept that altered patterns of infection during early childhood can deliver the necessary promotional drive for the progression of ETV6-RUNX1+ pre-leukaemic cells into a postnatal overt leukaemia.

  20. Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma

    Science.gov (United States)

    Kundu, Mondira; Compton, Sheila; Garrett-Beal, Lisa; Stacy, Terryl; Starost, Matthew F.; Eckhaus, Michael; Speck, Nancy A.; Liu, P. Paul

    2005-01-01

    Chromosomal rearrangements affecting RUNX1 and CBFB are common in acute leukemias. These mutations result in the expression of fusion proteins that act dominant-negatively to suppress the normal function of the Runt-related transcription factor 1 (RUNX)/core binding factor β (CBFβ) complexes. In addition, loss-of-function mutations in Runt-related transcription factor 1 (RUNX1) have been identified in sporadic cases of acute myeloid leukemia (AML) and in association with the familial platelet disorder with propensity to develop AML (FPD/AML). In order to examine the hypothesis that decreased gene dosage of RUNX1 may be a critical event in the development of leukemia, we treated chimeric mice generated from Runx1lacZ/lacZ embryonic stem (ES) cells that have homozygous disruption of the Runx1 gene with N-ethyl-N-nitrosourea (ENU). We observed an increased incidence of T-lymphoblastic lymphoma in Runx1lacZ/lacZ compared with wild-type chimeras and confirmed that the tumors were of ES-cell origin. Our results therefore suggest that deficiency of Runx1 can indeed predispose mice to hematopoietic malignancies. PMID:16051740

  1. The mystery of electroencephalography in acute lymphoblastic leukemia.

    Science.gov (United States)

    Goldberg-Stern, Hadassa; Cohen, Rony; Pollak, Lea; Kivity, Sara; Eidlitz-Markus, Tal; Stark, Batya; Yaniv, Isaac; Shuper, Avinoam

    2011-04-01

    The aim of the study was to evaluate changes in electroencephalogram (EEG) recordings during the course of acute lymphoblastic leukemia (ALL) in children. The study group consisted of 48 children with ALL who underwent a total of 72 EEGs at various stages of the disease. The medical files were reviewed for pertinent clinical data, and the EEGs were evaluated for changes in brain activity. Abnormal background activity was noted in 52.2% of the EEGs done at 1-10 days of therapy, in 43.5% of those done at 10-60 days, and only 4.3% of those done at later stages (p=0.037). These findings, together with earlier reports, suggest that early-stage ALL, even before treatment, may be associated with excessive slow EEG activity, which improves over time. The EEG changes, by themselves, are not an indication of central nervous system leukemia or a predictor of later seizures or other central nervous system involvement.

  2. Management of Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Ottmann, O G

    2012-08-01

    Tyrosine kinase inhibitors (TKIs) directed against the ABL kinase are now used routinely during frontline therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) and result in hematologic remission rates exceeding 90%. Minimal residual disease levels are generally lower when TKIs are used in combination with chemotherapy rather than as monotherapy. Although outcome has improved substantially with TKI-based regimens compared with historic controls, allogeneic stem cell transplantation (SCT) in first remission provides the best chance of cure for the majority of patients eligible for SCT. Administration of imatinib after SCT further reduces molecular recurrence and is associated with greatly improved relapse-free and overall survival. The high relapse rate in non-transplanted patients is largely attributable to the emergence of leukemic clones with mutations in the tyrosine kinase domain of BCR-ABL. Ongoing studies with newer TKIs will determine whether these more potent agents are able to sustain remissions without SCT. Assessment of minimal residual disease has become an integral part of the management of Ph+ALL, as it has prognostic importance and is used to guide therapeutic intervention. Novel immunotherapeutic interventions and combinations of TKIs are currently being investigated in clinical trials and may further improve the prognosis of patients with Ph+ALL.

  3. Acute Lymphoblastic Leukemia with Eosinophilia and Strongyloides Stercoralis Hyperinfection

    Directory of Open Access Journals (Sweden)

    Yadollah Zahedpasha

    2011-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in children. Bone pain is an important symptom that can be severe. Eosinophilia without any other abnormal laboratory findings is rare in ALL. Strongyloides stercoralis in ALL causes disseminated fatal disease.Case Presentation: This 9-year-old girl presented with bone pain in lumbar region. Bone pain was the only symptom. The patient didnt have organomegaly. The BM samples were studied by flow cytometry, which showed pre-B cell ALL. Larva of Strongyloides stercoralis was found in fecal examination. Plain chest x ray showed bilateral para-cardiac infiltration. Strongyloidiasis was treated before starting chemotherapy. After two days treatment with Mebendazol the patient developed cough, dyspnea, respiratory distress and fever. The treatment changed to Ivermectin for 2 days. Chemotherapy started five days after diagnosis of leukemia.Conclusion: The patient complained merely of bone pain in lumbar region without any other signs and symptoms. Peripheral blood smear showed eosinophilia without any other abnormality. Stool examination showed Strongyloides stercoralis larvae. We suggest that all patients diagnosed as ALL in tropical and subtropical regions should be evaluated for parasitic infection especially with Strongyloides stercoralis.

  4. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia.

    Science.gov (United States)

    Raj, Trisha A Soosay; Smith, Amanda M; Moore, Andrew S

    2013-01-01

    Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI]) formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR-ABL1) (Ph)-negative (Ph-) disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+) and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.

  5. Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mehta, Parinda A.; Zhang, Mei-Jie; Eapen, Mary; He, Wensheng; Seber, Adriana; Gibson, Brenda; Camitta, Bruce M.; Kitko, Carrie L.; Dvorak, Christopher C.; Nemecek, Eneida R.; Frangoul, Haydar A.; Abdel-Azim, Hisham; Kasow, Kimberly A.; Lehmann, Leslie; Vicent, Marta Gonzalez; Diaz Pérez, Miguel A.; Ayas, Mouhab; Qayed, Muna; Carpenter, Paul A.; Jodele, Sonata; Lund, Troy C.; Leung, Wing H.; Davies, Stella M.

    2015-01-01

    Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplant (HSCT) between 1990 and 2010. Thirty nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes and 27 (35%) had 45 chromosomes. Forty three (55%) patients were transplanted in first remission (CR1) while 35 (45%) were transplanted in ≥CR2. Twenty nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival (LFS), overall survival (OS), relapse, and treatment related mortality (TRM) for the entire cohort were 51%, 56%, 27% and 22% respectively. Multivariate analysis confirmed that mortality risks were higher for patients transplanted in CR2 (HR 2.16, p=0.05), with chromosome number ≤43 (HR 2.15, p=0.05) and for those transplanted in the first decade of the study period (HR 2.60, p=0.01). Similarly, treatment failure risks were higher with chromosome number ≤43 (HR 2.28, p=0.04) and the earlier transplant period (HR 2.51, p=0.01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes. PMID:25865650

  6. Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Stanković Tatjana

    2008-01-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common paediatric cancer. Despite cure rates approaching 80%, resistance to treatment and disease relapse remain a significant clinical problem. Identification of the genes and biological pathways responsible for chemoresistance is therefore crucial for the design of novel therapeutic approaches aiming to improve patient survival. Mutations in the membrane transporter P-glycoprotein genes, genetic variations in drug-metabolising enzymes and defects in apoptotic pathways are mechanisms of chemoresistance common to a wide spectrum of cancers and also play a role in paediatric ALL. In addition, several recent microarray studies have identified transcriptional profiles specifically associated with chemoresistance and pointed to a number of potentially novel therapeutic targets. These microarray studies have shown that genes discriminating between clinically responsive and resistant leukaemias tend to be involved in cellular processes such as regulation of cell cycle, proliferation, and DNA repair. Here we review the outcomes of these microarray studies and also present our own investigations into apoptotic resistance to DNA double strand breaks (DSBs in paediatric ALL. We present stratification of paediatric ALL by the profile of DNA damage response following ionising radiation (IR in vitro. This approach allows classification of ALL tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant. Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB pathway following irradiation and inhibition of this pathway can sensitise leukaemic cells to IR-induced DSBs.

  7. Infant acute lymphoblastic leukemia: a 20-year children's hospital experience.

    Science.gov (United States)

    Murray, Rebecca A F; Thom, Giddel; Gardner, Renee V; Craver, Randall D

    2008-01-01

    We reviewed our 20-year experience with infant acute lymphoblastic leukemia (ALL). Nine infants (4.2% of all ALL) were identified; all were < 6 months of age. White blood cell counts ranged from 42,000-1.6 million/microL, 6 of 8 had hepatosplenomegaly, and 6 of 9 (66.6%) had central nervous system disease. Of 7 with cytogenetic information, 6 (85.7%) had diploidy; the remaining child was 47, XY,+8,del(21)(q22). Four had the MLL-11q23 abnormality. All received chemotherapy. Four underwent stem cell transplantation. Survival was 67%, (15 months-21 years). Deaths occurred at 9 months, 15 months (graft vs. host), and 7 years (complications of small bowel transplantation). Only 1 undergoing stem cell transplantation died. There were no late recurrences or second malignancies. Despite extensive disease and age < 6 months at diagnosis (a poor prognostic feature), for ALL patients our 67% survival is at least as good as reported, although it is less favorable than childhood ALL.

  8. The genomic landscape of hypodiploid acute lymphoblastic leukemia.

    Science.gov (United States)

    Holmfeldt, Linda; Wei, Lei; Diaz-Flores, Ernesto; Walsh, Michael; Zhang, Jinghui; Ding, Li; Payne-Turner, Debbie; Churchman, Michelle; Andersson, Anna; Chen, Shann-Ching; McCastlain, Kelly; Becksfort, Jared; Ma, Jing; Wu, Gang; Patel, Samir N; Heatley, Susan L; Phillips, Letha A; Song, Guangchun; Easton, John; Parker, Matthew; Chen, Xiang; Rusch, Michael; Boggs, Kristy; Vadodaria, Bhavin; Hedlund, Erin; Drenberg, Christina; Baker, Sharyn; Pei, Deqing; Cheng, Cheng; Huether, Robert; Lu, Charles; Fulton, Robert S; Fulton, Lucinda L; Tabib, Yashodhan; Dooling, David J; Ochoa, Kerri; Minden, Mark; Lewis, Ian D; To, L Bik; Marlton, Paula; Roberts, Andrew W; Raca, Gordana; Stock, Wendy; Neale, Geoffrey; Drexler, Hans G; Dickins, Ross A; Ellison, David W; Shurtleff, Sheila A; Pui, Ching-Hon; Ribeiro, Raul C; Devidas, Meenakshi; Carroll, Andrew J; Heerema, Nyla A; Wood, Brent; Borowitz, Michael J; Gastier-Foster, Julie M; Raimondi, Susana C; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Hunger, Stephen P; Loh, Mignon L; Mullighan, Charles G

    2013-03-01

    The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.

  9. Suppressed neutrophil function in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Tanaka, Fumiko; Goto, Hiroaki; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Kajiwara, Ryosuke; Naruto, Takuya; Nishimaki, Shigeru; Yokota, Shumpei

    2009-10-01

    Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 +/- 13.2 or 70.0 +/- 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 +/- 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.

  10. Is this acute lymphoblastic leukaemia or juvenile rheumatoid arthritis.

    Science.gov (United States)

    Kirubakaran, Chellam; Scott, Julius Xavier; Ebenezer, Sam

    2011-08-01

    Arthritis could be a presenting feature of acute lymphoblastic leukaemia (ALL) and could be wrongly diagnosed as juvenile rheumatoid arthritis (JRA). Clinical and laboratory parameters might differentiate ALL and JRA in children who present with arthritis. Out of a total of 250 children of ALL, 10 were referred to the department of child health and paediatric haemato-oncology of Christian Medical College, Vellore during 1990-2002. They were compared with 10 age-matched children who had systematic onset of JRA. The age groups in ALL and JRA were 6.05 +/- 2.45 years and 5.47 +/- 4.4 years respectively. Severe pain as evidenced by inability to walk was found in children but one child with JRA was unable to walk (p JRA group. ESR was elevated in all cases in both the groups. One case in each group had antinuclear antibody positivity. It can be concluded that ALL can masquerade as systematic onset of JRA. So paediatricians should be careful enough while diagnosing the disease process.

  11. TREATMENT OF ADOLESCENT AND YOUNG ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Josep-Maria Ribera

    2014-07-01

    Full Text Available The primary objective of this review was to update and discuss the current concepts andthe results of the treatment of acute lymphoblastic leukemia (ALL in adolescents and young adults(AYA. After a brief consideration of the epidemiologic and clinicobiologic characteristics of ALLin the AYA population, the main retrospective comparative studies stating the superiority ofpediatric over adult-based protocols were reviewed. The most important prospective studies inyoung adults using pediatric inspired or pediatric unmodified protocols were also reviewedemphasizing their feasibility at least up to the age of 40 yr and their promising results, with eventfreesurvival rates of 60-65% or greater. Results of trials from pediatric groups have shown that theunfavourable prognosis of adolescents is no more adequate. The majority of the older adolescentswith ALL can be cured with risk-adjusted and minimal residual disease-guided intensivechemotherapy, without stem cell transplantation. However, some specific subgroups, which aremore frequent in adolescents than in children (e.g., early pre-T, iAMP21, and BCR-ABL-like,deserve particular attention. In summary, the advances in treatment of ALL in adolescents havebeen translated to young adults, and that explains the significant improvement in survival of thesepatients in recent years.

  12. A 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Pui, Ching-Hon; Evans, William E.

    2013-01-01

    The 50th anniversary of Seminars in Hematology coincides with the 50th of St. Jude Children’s Research Hospital, and both milestones are inexorably linked to studies contributing to the cure of childhood acute lymphoblastic leukemia (ALL). We thought it fitting, therefore, to mark these events by traveling back in time to point out some of the achievements, institutions, study groups and individuals that have made cure of childhood ALL a reality. In many instances, progress was driven by new ideas, while in others it was driven by new experimental tools that allowed more precise assessment of the biology of leukemic blasts and their utility in selecting therapy. We also discuss a number of contemporary advances that point the way to exciting future directions. Whatever pathways are taken, a clear challenge will be to use emerging genome-based or immunologic-based treatment options in ways that will enhance, rather than duplicate or compromise, recent gains in outcome with classic cytotoxic chemotherapy. The theme of this journey serves as a reminder of the chief ingredient of any research directed to a catastrophic disease such as ALL. It is the audacity of a small group of investigators who confronted a childhood cancer with the goal of cure, not palliation, as their mindset. PMID:23953334

  13. Invasive Pulmonary Aspergillosis in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Orhan Ayyıldız

    2004-01-01

    Full Text Available Fungal infections are common and life-threatening among immunosupressive patients.Invasive pulmonar aspergilloz (IPA generally occurs when Aspergillus inhaled, but rarelywith the hematogen spread of dermal or gastrointestinal Aspergillus. We present here, IPA ina 58 year-old male patient with acute lymphoblastic leukemia (ALL. He was admitted to ourclinic with fatigue, weakness, pansitopenia, and with petechia. Supportive treatment,vincristine and prednisone was initiated. Chest roentgenogram was normal. Dyspnea andfever (39.5’C were seen after 1 month of therapy. Thorax high resolution computerizedtomography was obtained and cavitary lesion was seen in the left upper-anterior segment oflung. Sputum and blood culture were negative. In spite of the empiric use of Meropenem 3gr/d, Vancomycin 2 gr/d and fluconazole 200 mg/d, fever was not turned to normal andclinical symptoms were not healed. On the fifth days of therapy amphotericin-B was initiatedand the other antibiotics were stopped after 3 days. General symptoms were healed on the 8thdays. Radiologic findings were improved partially after 20 days. The patient clinically is welland remains in remission and radiologic findings were turn to near normal after 10 monthsof treatment. We aimed to emphasis about treatment of empirical Amphotericin-B incritically ill patient with ALL.

  14. Critical mutation rate has an exponential dependence on population size in haploid and diploid populations.

    Science.gov (United States)

    Aston, Elizabeth; Channon, Alastair; Day, Charles; Knight, Christopher G

    2013-01-01

    Understanding the effect of population size on the key parameters of evolution is particularly important for populations nearing extinction. There are evolutionary pressures to evolve sequences that are both fit and robust. At high mutation rates, individuals with greater mutational robustness can outcompete those with higher fitness. This is survival-of-the-flattest, and has been observed in digital organisms, theoretically, in simulated RNA evolution, and in RNA viruses. We introduce an algorithmic method capable of determining the relationship between population size, the critical mutation rate at which individuals with greater robustness to mutation are favoured over individuals with greater fitness, and the error threshold. Verification for this method is provided against analytical models for the error threshold. We show that the critical mutation rate for increasing haploid population sizes can be approximated by an exponential function, with much lower mutation rates tolerated by small populations. This is in contrast to previous studies which identified that critical mutation rate was independent of population size. The algorithm is extended to diploid populations in a system modelled on the biological process of meiosis. The results confirm that the relationship remains exponential, but show that both the critical mutation rate and error threshold are lower for diploids, rather than higher as might have been expected. Analyzing the transition from critical mutation rate to error threshold provides an improved definition of critical mutation rate. Natural populations with their numbers in decline can be expected to lose genetic material in line with the exponential model, accelerating and potentially irreversibly advancing their decline, and this could potentially affect extinction, recovery and population management strategy. The effect of population size is particularly strong in small populations with 100 individuals or less; the exponential model has

  15. Genomic incompatibilities in the diploid and tetraploid offspring of the goldfish × common carp cross.

    Science.gov (United States)

    Liu, Shaojun; Luo, Jing; Chai, Jing; Ren, Li; Zhou, Yi; Huang, Feng; Liu, Xiaochuan; Chen, Yubao; Zhang, Chun; Tao, Min; Lu, Bin; Zhou, Wei; Lin, Guoliang; Mai, Chao; Yuan, Shuo; Wang, Jun; Li, Tao; Qin, Qinbo; Feng, Hao; Luo, Kaikun; Xiao, Jun; Zhong, Huan; Zhao, Rurong; Duan, Wei; Song, Zhenyan; Wang, Yanqin; Wang, Jing; Zhong, Li; Wang, Lu; Ding, Zhaoli; Du, Zhenglin; Lu, Xuemei; Gao, Yun; Murphy, Robert W; Liu, Yun; Meyer, Axel; Zhang, Ya-Ping

    2016-02-02

    Polyploidy is much rarer in animals than in plants but it is not known why. The outcome of combining two genomes in vertebrates remains unpredictable, especially because polyploidization seldom shows positive effects and more often results in lethal consequences because viable gametes fail to form during meiosis. Fortunately, the goldfish (maternal) × common carp (paternal) hybrids have reproduced successfully up to generation 22, and this hybrid lineage permits an investigation into the genomics of hybridization and tetraploidization. The first two generations of these hybrids are diploids, and subsequent generations are tetraploids. Liver transcriptomes from four generations and their progenitors reveal chimeric genes (>9%) and mutations of orthologous genes. Characterizations of 18 randomly chosen genes from genomic DNA and cDNA confirm the chimera. Some of the chimeric and differentially expressed genes relate to mutagenesis, repair, and cancer-related pathways in 2nF1. Erroneous DNA excision between homologous parental genes may drive the high percentage of chimeric genes, or even more potential mechanisms may result in this phenomenon. Meanwhile, diploid offspring show paternal-biased expression, yet tetraploids show maternal-biased expression. These discoveries reveal that fast and unstable changes are mainly deleterious at the level of transcriptomes although some offspring still survive their genomic abnormalities. In addition, the synthetic effect of genome shock might have resulted in greatly reduced viability of 2nF2 hybrid offspring. The goldfish × common carp hybrids constitute an ideal system for unveiling the consequences of intergenomic interactions in hybrid vertebrate genomes and their fertility.

  16. Transcriptome Analysis of Honeybee (Apis Mellifera) Haploid and Diploid Embryos Reveals Early Zygotic Transcription during Cleavage

    Science.gov (United States)

    Pires, Camilla Valente; Freitas, Flávia Cristina de Paula; Cristino, Alexandre S.; Dearden, Peter K.; Simões, Zilá Luz Paulino

    2016-01-01

    In honeybees, the haplodiploid sex determination system promotes a unique embryogenesis process wherein females develop from fertilized eggs and males develop from unfertilized eggs. However, the developmental strategies of honeybees during early embryogenesis are virtually unknown. Similar to most animals, the honeybee oocytes are supplied with proteins and regulatory elements that support early embryogenesis. As the embryo develops, the zygotic genome is activated and zygotic products gradually replace the preloaded maternal material. The analysis of small RNA and mRNA libraries of mature oocytes and embryos originated from fertilized and unfertilized eggs has allowed us to explore the gene expression dynamics in the first steps of development and during the maternal-to-zygotic transition (MZT). We localized a short sequence motif identified as TAGteam motif and hypothesized to play a similar role in honeybees as in fruit flies, which includes the timing of early zygotic expression (MZT), a function sustained by the presence of the zelda ortholog, which is the main regulator of genome activation. Predicted microRNA (miRNA)-target interactions indicated that there were specific regulators of haploid and diploid embryonic development and an overlap of maternal and zygotic gene expression during the early steps of embryogenesis. Although a number of functions are highly conserved during the early steps of honeybee embryogenesis, the results showed that zygotic genome activation occurs earlier in honeybees than in Drosophila based on the presence of three primary miRNAs (pri-miRNAs) (ame-mir-375, ame-mir-34 and ame-mir-263b) during the cleavage stage in haploid and diploid embryonic development. PMID:26751956

  17. Efficient production of tetraploid barley (Hordeum vulgare L. by colchicine treatment of diploid barley

    Directory of Open Access Journals (Sweden)

    Ayed Sourour

    2014-03-01

    Full Text Available An experiment was conducted to induce tetraploidy in three diploid barley varieties (Martin, Rihane and Manel through different colchicines treatments. Colchicine was added for three different concentrations at three different stages of plant development i.e. on seed (0.05% for 48 hours, on pre-germinated seeds (0.1% for 2 hours and on three leaf stage (0.1% for 16 hours. Colchicine application reduced significantly germination percentage and viability of plants. Seed germination was completely inhibited in Martin, while a reduction of 20% and 30% for germination percentage compared to control was recorded in varieties Manel and Rihane, respectively at 0.1% colchicine concentration. Ploidy evaluation showed no tetraploidy in all the three tested varieties by colchicine application of 0.05% for 48 hours on seeds and 0.1% for 2 hours on pre-germinated seeds. However, tetraploid plants were produced only by treatment with 0.1% for 16 hours of seedlings. The percentages of plants were 40%, 44% and 100% for Rihane, Manel and Martin, respectively. Cytological analyses showed the increase of chromosome numbers from 2n=2x=14 to 2n=4x=28. The increase of ploidy levels caused major changes in some morphological traits. In fact, the induced tetraploids in barley was accompanied by significant (P<0.01 decrease in plant height, tiller height, leaf number and leaf length compared to diploid control plants. colchicine treatment induce successfully the production of tetraploid barley plants and could be used in breeding programs.

  18. Phylogenetic relationships among diploid Aegilops species inferred from 5S rDNA units.

    Science.gov (United States)

    Baum, B R; Edwards, T; Johnson, D A

    2009-10-01

    Relationships among the currently recognized 11 diploid species within the genus Aegilops have been investigated. Sequence similarity analysis, based upon 363 sequenced 5S rDNA clones from 44 accessions plus 15 sequences retrieved from GenBank, depicted two unit classes labeled the long AE1 and short AE1. Several different analytical methods were applied to infer relationships within haplomes, between haplomes and among the species, including maximum parsimony and maximum likelihood analyses of consensus sequences, "total evidence" phylogeny analysis and "matrix representation with parsimony" analysis. None were able to depict suites of markers or unit classes that could discern among the seven haplomes as is observed among established haplomes in other genera within the tribe Triticeae; however, most species could be separated when displayed on gene trees. These results suggest that the haplomes currently recognized are so refined that they may be relegated as sub-haplomes or haplome variants. Amblyopyrum shares the same 5S rDNA unit classes with the diploid Aegilops species suggesting that it belongs within the latter. Comparisons of the Aegilops sequences with those of Triticum showed that the long AE1 unit class of Ae. tauschii shared the clade with the equivalent long D1 unit class, i.e., the putative D haplome donor, but the short AE1 unit class did not. The long AE1 unit class but not the short, of Ae. speltoides and Ae. searsii both share the clade with the previously identified long {S1 and long G1 unit classes meaning that both Aegilops species can be equally considered putative B haplome donors to tetraploid Triticum species. The semiconserved nature of the nontranscribed spacer in Aegilops and in Triticeae in general is discussed in view that it may have originated by processes of incomplete gene conversion or biased gene conversion or birth-and-death evolution.

  19. Unilateral Exudative Retinal Detachment as the Sole Presentation of Relapsing Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Azık

    2012-06-01

    Full Text Available Ocular findings are rarely the initial symptom of leukemia, although up to 90% of all leukemia patients have fundus changes during the course of the disease. Herein we report a relapsing acute lymphoblastic leukemia patient with the sole presentation of sudden visual loss and exudative retinal detachment. An 8-year-old boy with acute lymphoblastic leukemia developed sudden visual loss during his first remission period. Bullous retinal detachment with total afferent pupillary defect was observed. Orbital magnetic resonance imaging revealed an intraocular mass lesion; simultaneously obtained bone marrow and cerebrospinal fluid samples showed no evidence of leukemic cells. Following local irradiation, and systemic and intrathecal chemotherapy the mass disappeared. Local irradiation, and systemic and intrathecal chemotherapy effectively controlled the isolated ocular relapse of acute lymphoblastic leukemia and eliminated the need for enucleation.

  20. Acute hepatitis A induction of precursor B-cell acute lymphoblastic leukemia: a causal relationship?

    Science.gov (United States)

    Senadhi, V; Emuron, D; Gupta, R

    2010-09-01

    Precursor B-cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the United States and occurs most frequently in childhood, but can also occur in adults with a median age of 39 years. It is more commonly seen in males and in Caucasians. We present a case of a 51-year-old Caucasian female with the development of precursor B-cell acute lymphoblastic leukemia after suffering acute hepatitis A 4 weeks prior to her diagnosis. She presented with malaise for a month without spontaneous bruising/bleeding, infections, or B-symptoms, such as fevers, night sweats, or unintentional weight loss. Nonspecific viral transformation of bone marrow has been discussed in the literature, but we specifically describe hepatitis A-induced adult-onset precursor B-cell acute lymphoblastic leukemia, which is the first reported case in the literature.

  1. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi...... method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis......, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14...

  2. The importance of immunophenotyping by flow cytometry in distinction between hematogones and B lymphoblasts

    Directory of Open Access Journals (Sweden)

    Aline B. Wohlfahrt

    2015-02-01

    Full Text Available Hematogones are normal B-lineage lymphoid precursors in the bone marrow. B lymphoblasts are immature neoplastic cells present in patients with precursor B-cell acute lymphoblastic leukemia (B-ALL. Hematogones and B lymphoblasts share characteristics, such as morphological similarity often indistinct and expression of the same antigens in immunophenotypic analysis. Increased numbers of hematogones in patients with B-ALL during regeneration of bone marrow after treatment for leukemia, in cases of disease relapse or marrow transplantation, may be subject to questions about the nature and prognosis of this immature cell. This article presents information about the morphological and immunophenotypic characteristics of B lymphoid precursors and verifies the relevance of immunophenotyping by flow cytometry (FC in the distinction between those cells. This differentiation is essential to establish a correct prognosis and assist in medical decision about the most appropriate therapeutic scheme.

  3. Cultivation of diploid and tetraploid hairy roots of Datura stramonium L. in stirred tank bioreactor for tropane alkaloids production

    Directory of Open Access Journals (Sweden)

    ATANAS PAVLOV

    2012-01-01

    Full Text Available Biomass accumulation and tropane alkaloids production by diploid and tetraploid hairy root cultures of Datura stramonium L. cultivated in stirred tank bioreactor at different aeration rates were investigated. The maximal growth for both hairy root cultures (ADB = 8.3 g/L and 6.8 g/L for diploid and tetraploid line, respectively was achieved at aeration rate of 15.0 L/(L.h. The corresponding growth indexes were remarkably high (GIDW = 9.0 and 7.8 for diploid and tetraploid line, respectively compared to the values, usually reported for other hairy root cultures. The optimal aeration rate for biomass accumulation was also optimal for alkaloids biosynthesis. According to our survey, the achieved maximal amounts of accumulated hyoscyamine (35.0 mg/L and 27.0 mg/L for diploid and tetraploid line were the highest reported in the scientific literature for D. stramonium L. hairy roots. During the cultivation in stirred tank bioreactor, the hairy roots biosynthesized pharmaceutically important alkaloid scopolamine in minor concentrations. This is an important observation since scopolamine was not detected during submerged cultivation of these hairy root lines in other bioreactor types. However, the ploidy level was found to be the most important factor concerning scopolamine production by D. stramonium L. hairy roots cultures. The present work demonstrated the effect of ploidity levels on biomass accumulation and tropane alkaloids production by D. stramonium L. hairy roots cultivated in stirred tank bioreactor. This investigation show that the stirred tank bioreactor could be successfully applied for both maximal biomass accumulations, as well as for manipulation of tropane alkaloids production by diploid and tetraploid D. stramonium L. hairy root cultures.

  4. Genome-wide mutation avalanches induced in diploid yeast cells by a base analog or an APOBEC deaminase.

    Directory of Open Access Journals (Sweden)

    Artem G Lada

    Full Text Available Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis.

  5. Direct ethanol production from cellulosic materials using a diploid strain of Saccharomyces cerevisiae with optimized cellulase expression

    Directory of Open Access Journals (Sweden)

    Fukuda Hideki

    2011-04-01

    Full Text Available Abstract Background Hydrolysis of cellulose requires the action of the cellulolytic enzymes endoglucanase, cellobiohydrolase and β-glucosidase. The expression ratios and synergetic effects of these enzymes significantly influence the extent and specific rate of cellulose degradation. In this study, using our previously developed method to optimize cellulase-expression levels in yeast, we constructed a diploid Saccharomyces cerevisiae strain optimized for expression of cellulolytic enzymes, and attempted to improve the cellulose-degradation activity and enable direct ethanol production from rice straw, one of the most abundant sources of lignocellulosic biomass. Results The engineered diploid strain, which contained multiple copies of three cellulase genes integrated into its genome, was precultured in molasses medium (381.4 mU/g wet cell, and displayed approximately six-fold higher phosphoric acid swollen cellulose (PASC degradation activity than the parent haploid strain (63.5 mU/g wet cell. When used to ferment PASC, the diploid strain produced 7.6 g/l ethanol in 72 hours, with an ethanol yield that achieved 75% of the theoretical value, and also produced 7.5 g/l ethanol from pretreated rice straw in 72 hours. Conclusions We have developed diploid yeast strain optimized for expression of cellulolytic enzymes, which is capable of directly fermenting from cellulosic materials. Although this is a proof-of-concept study, it is to our knowledge, the first report of ethanol production from agricultural waste biomass using cellulolytic enzyme-expressing yeast without the addition of exogenous enzymes. Our results suggest that combining multigene expression optimization and diploidization in yeast is a promising approach for enhancing ethanol production from various types of lignocellulosic biomass.

  6. Transplantation of marrow cells from children with standard risk-acute lymphoblastic leukemia at the end of therapy into NOD/SCID mice for detecting residual leukemic cells with in vivo growth potential.

    Science.gov (United States)

    Ramírez, Manuel; Díaz, Miguel A; Madero, Luis; Bueren, Juan A

    2003-12-01

    In the present work, we developed a strategy for detecting residual leukemia in the marrow of children with standard risk-acute lymphoblastic leukemia (sr-ALL) at the end of therapy, based on the capacity of human leukemic cells for growing in the NOD/SCID mice marrow microenvironment. Mononuclear (MN) marrow cells from 62 patients were injected into sublethally irradiated NOD/SCID mice and the engraftment kinetics and composition of the human grafts were determined periodically. The presence of human leukemic cells with immunophenotypes and clonal DNA markers similar to those of the original leukemic clone was studied.

  7. Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

    Science.gov (United States)

    Labar, Boris; Suciu, Stefan; Willemze, Roel; Muus, Petra; Marie, Jean-Pierre; Fillet, Georges; Berneman, Zwi; Jaksic, Branimir; Feremans, Walter; Bron, Dominique; Sinnige, Harm; Mistrik, Martin; Vreugdenhil, Gerard; De Bock, Robrecht; Nemet, Damir; Gilotay, Caroline; Amadori, Sergio; de Witte, Theo

    2010-01-01

    Background Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone. Design and Methods Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1–8 and 15–22, either dexamethasone 8 mg/m2 or prednisolone 60 mg/m2. Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis. Results Between August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75–1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76–1.40). The 6-year cumulative

  8. Acute lymphoblastic leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available of the trial TropicALL study; Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with L...oprofylaxe in kinderen behandeld voor Acute lymfatische leukemie met laag-moleculair-gewicht heparine: een g...dition or disease under investigation E.1.1Medical condition(s) being investigated Acute lymphoblastic leukemia Acute... Medical condition or disease under investigation E.1.2Version 17.1 E.1.2Level LLT E.1.2Classification code 10000845 E.1.2Term Acute

  9. UNUSUAL CLINICAL PRESENTATION OF RELAPSE IN PATIENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA.

    Directory of Open Access Journals (Sweden)

    Vanya Slavcheva

    2015-04-01

    Full Text Available Acute lymphoblastic leukemia is a disease, which is more common in children. We report a clinical case of a patient aged 25. Thirty-two months before his last admission in Hematology clinic, acute pre- B lymphoblastic leukemia had been diagnosed and treated till March 2012. In September 2013 after bone marrow aspiration, flow cytometric analysis, trepan biopsy and biopsy of the kidney had been carried out, the patient was diagnosed with first late relapse, involving bone marrow and kidney. A second remission was achieved using Berlin- Frankfurt– Munster chemotherapy [BFM] and allogenic stem cell transplantation was performed.

  10. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

  11. Primary lymphoblastic B-cell lymphoma of the stomach: A case report

    Institute of Scientific and Technical Information of China (English)

    Miao-Xia He; Ming-Hua Zhu; Wei-Qiang Liu; Li-Li Wu; Xiong-Zeng Zhu

    2008-01-01

    Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo.Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site.Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.

  12. I. Effect of Trichinella spiralis infection on the migration of mesenteric lymphoblasts and mesenteric T lymphoblasts in syngeneic mice.

    Science.gov (United States)

    Rose, M L; Parrott, D M; Bruce, R G

    1976-11-01

    The migration of [125I]UdR-labelled mesenteric lymph node cells in NIH strain mice at various times after inis produced an enhanced accumulation of mesenteric immunoblasts in the small intestine at 2 and 4 days after infection but not at later times. The enhanced migration occurred when using cells from both uninfected and infected donors, denoting an absence of antigenic specificity. This effect is not secondary to a reduced arrival of cells at sites away from the gut in infected mice, but to a primary increase of the arrival in the small intestine. Mesenteric T lymphoblasts (separated on a nylon-wool column) migrated to the small intestine of uninfected recipients and appear to be a major portion of the population which migrate to the gut of infected recipients. Our results were confirmed using 51Cr to label mesenteric cells. We conclude that the parasite causes the small intestine to become more attractive or retentive for mesenteric blast cells early during infection.

  13. Transcript levels of ten caste-related genes in adult diploid males of Melipona quadrifasciata (Hymenoptera, Apidae: a comparison with haploid males, queens and workers

    Directory of Open Access Journals (Sweden)

    Andreia A. Borges

    2011-01-01

    Full Text Available In Hymenoptera, homozygosity at the sex locus results in the production of diploid males. In social species, these pose a double burden by having low fitness and drawing resources normally spent for increasing the work force of a colony. Yet, diploid males are of academic interest as they can elucidate effects of ploidy (normal males are haploid, whereas the female castes, the queens and workers, are diploid on morphology and life history. Herein we investigated expression levels of ten caste-related genes in the stingless bee Melipona quadrifasciata, comparing newly emerged and 5-day-old diploid males with haploid males, queens and workers. In diploid males, transcript levels for dunce and paramyosin were increased during the first five days of adult life, while those for diacylglycerol kinase and the transcriptional co-repressor groucho diminished. Two general trends were apparent, (i gene expression patterns in diploid males were overall more similar to haploid ones and workers than to queens, and (ii in queens and workers, more genes were up-regulated after emergence until day five, whereas in diploid and especially so in haploid males more genes were down-regulated. This difference between the sexes may be related to longevity, which is much longer in females than in males.

  14. A new synthetic allotetraploid (A1A1G2G2 between Gossypium herbaceum and G. australe: bridging for simultaneously transferring favorable genes from these two diploid species into upland cotton.

    Directory of Open Access Journals (Sweden)

    Quan Liu

    Full Text Available Gossypium herbaceum, a cultivated diploid cotton species (2n = 2x = 26, A1A1, has favorable traits such as excellent drought tolerance and resistance to sucking insects and leaf curl virus. G. australe, a wild diploid cotton species (2n = 2x = 26, G2G2, possesses numerous economically valuable characteristics such as delayed pigment gland morphogenesis (which is conducive to the production of seeds with very low levels of gossypol as a potential food source for humans and animals and resistance to insects, wilt diseases and abiotic stress. Creating synthetic allotetraploid cotton from these two species would lay the foundation for simultaneously transferring favorable genes into cultivated tetraploid cotton. Here, we crossed G. herbaceum (as the maternal parent with G. australe to produce an F1 interspecific hybrid and doubled its chromosome complement with colchicine, successfully generating a synthetic tetraploid. The obtained tetraploid was confirmed by morphology, cytology and molecular markers and then self-pollinated. The S1 seedlings derived from this tetraploid gradually became flavescent after emergence of the fifth true leaf, but they were rescued by grafting and produced S2 seeds. The rescued S1 plants were partially fertile due to the existence of univalents at Metaphase I of meiosis, leading to the formation of unbalanced, nonviable gametes lacking complete sets of chromosomes. The S2 plants grew well and no flavescence was observed, implying that interspecific incompatibility, to some extent, had been alleviated in the S2 generation. The synthetic allotetraploid will be quite useful for polyploidy evolutionary studies and as a bridge for transferring favorable genes from these two diploid species into Upland cotton through hybridization.

  15. Redox active copper chelate overcomes multidrug resistance in T-lymphoblastic leukemia cell by triggering apoptosis.

    Science.gov (United States)

    Ganguly, Avishek; Basu, Soumya; Banerjee, Kaushik; Chakraborty, Paramita; Sarkar, Avijit; Chatterjee, Mitali; Chaudhuri, Soumitra Kumar

    2011-05-01

    Multidrug resistance (MDR) mediated by the over expression of drug efflux protein P-glycoprotein (P-gp) is one of the major impediments to successful treatment of cancer. P-gp acts as an energy-dependent drug efflux pump and reduces the intracellular concentration of structurally unrelated drugs inside the cells. Therefore, there is an urgent need for development of new molecules that are less toxic to normal cell and preferentially effective against drug resistant malignant cells. In this preclinical study we report the apoptotic potential of copper N-(2-hydroxyacetophenone) glycinate (CuNG) on doxorubicin resistant T lymphoblastic leukaemia cells (CEM/ADR5000). To evaluate the cytotoxic effect of CuNG, we used different normal cell lines (NIH 3T3, Chang liver and human PBMC) and cancerous cell lines (CEM/ADR5000, parental sensitive CCRF-CEM, SiHa and 3LL) and conclude that CuNG preferentially kills cancerous cells, especially both leukemic cell types irrespective of their MDR status, while leaving normal cell totally unaffected. Moreover, CuNG involves reactive oxygen species (ROS) for induction of apoptosis in CEM/ADR5000 cells through the intrinsic apoptotic pathway. This is substantiated by our observation that antioxidant N-acetyle-cysteine (NAC) and PEG catalase could completely block ROS generation and, subsequently, abrogates CuNG induced apoptosis. On the other hand, uncomplexed ligand N-(2-hydroxyacetophenone) glycinate (NG) fails to generate a significant amount of ROS and concomitant induction of apoptosis in CEM/ADR5000 cells. Therefore, CuNG induces drug resistant leukemia cells to undergo apoptosis and proves to be a molecule having therapeutic potential to overcome MDR in cancer.

  16. The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Vercruysse, Thomas; De Bie, Jolien; Neggers, Jasper E; Jacquemyn, Maarten; Vanstreels, Els; Schmid-Burgk, Jonathan L; Hornung, Veit; Baloglu, Erkan; Landesman, Yosef; Senapedis, William; Shacham, Sharon; Dagklis, Antonis; Cools, Jan; Daelemans, Dirk

    2016-10-25

    Purpose: Human exportin-1 (XPO1) is the key nuclear-cytoplasmic transport protein that exports different cargo proteins out of the nucleus. Inducing nuclear accumulation of these proteins by inhibiting XPO1 causes cancer cell death. First clinical validation of pharmacological inhibition of XPO1 was obtained with the Selective Inhibitor of Nuclear Export (SINE) compound selinexor (KPT-330) demonstrating activity in phase-II/IIb clinical trials when dosed 1 to 3 times weekly. The second-generation SINE compound KPT-8602 shows improved tolerability and can be dosed daily. Here, we investigate and validate the drug-target interaction of KPT-8602 and explore its activity against acute lymphoblastic leukemia (ALL).Experimental Design: We examined the effect of KPT-8602 on XPO1 function and XPO1-cargo as well as on a panel of leukemia cell lines. Mutant XPO1 leukemia cells were designed to validate KPT-8602's drug-target interaction. In vivo, anti-ALL activity was measured in a mouse ALL model and patient-derived ALL xenograft models.Results: KPT-8602 induced caspase-dependent apoptosis in a panel of leukemic cell lines in vitro Using CRISPR/Cas9 genome editing, we demonstrated the specificity of KPT-8602 for cysteine 528 in the cargo-binding groove of XPO1 and validated the drug target interaction. In vivo, KPT-8602 showed potent anti-leukemia activity in a mouse ALL model as well as in patient-derived T- and B-ALL xenograft models without affecting normal hematopoiesis.Conclusions: KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of ALL. Clin Cancer Res; 1-14. ©2016 AACR.

  17. Severe Hypertriglyceridemia During Therapy For Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B.; Chemaitilly, Wassim; Sandlund, John T.; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V.; Jeha, Sima; Metzger, Monika L.

    2014-01-01

    Background Asparaginase and steroids can cause hypertriglyceridemia in children with acute lymphoblastic leukemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridemia (>1000 mg/dL) during ALL therapy. Patients and Methods Fasting lipid profiles were obtained prospectively at 4 time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridemia were extracted retrospectively. Results Eighteen of 257 (7%) patients developed severe hypertriglyceridemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridemia had a 2.5 to 3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistical significant. Of the 30 episodes of severe hypertriglyceridemia in 18 patients, 7 were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalized after completion of ALL therapy in all 12 patients with available measurements. Conclusion Asparaginase- and steroid-induced transient hypertriglyceridemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. PMID:25087182

  18. Temporal lobe epilepsy with hippocampal sclerosis in acute lymphoblastic leukemia.

    Science.gov (United States)

    Kasai-Yoshida, Emi; Ogihara, Masaaki; Ozawa, Miwa; Nozaki, Taiki; Morino, Michiharu; Manabe, Atsushi; Hosoya, Ryota

    2013-07-01

    Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.

  19. Cytologic Phenotypes of B-Cell Acute Lymphoblastic Leukemia-

    Directory of Open Access Journals (Sweden)

    Ramyar Asghar

    2009-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a malignant disorder of lymphoid precursor cells, which could be classified according to morphological and cytochemical methods as well as immunophenotyping. Twenty patients with ALL, who had been referred to the Children's Medical Center Hospital, during the year 2007, were enrolled in this study in order to evaluate the morphologic and immunophenotypic profile of these patients. Cytologic analysis of blood and bone marrow samples revealed that the frequency of ALL-L1 was 70%, followed by ALL-L2 and ALL-L3. The onset age of the patients with ALL-L1 was significantly lower than the patients with L2/L3. Severe anemia was significantly detected more in L1 group. Flow cytometic study of bone marrow showed that 10 cases had Pre-B1 ALL and 7 cases had Pre-B2 ALL, while three cases had Pro-B ALL. Comparisons of the characteristics and clinical manifestations among these groups did not show any appreciable difference. There were an increase percentage of CD20+ cells and a decrease CD10+ cells in pre-B2 group in comparison with pre-B1 group. Fifteen patients were in standard risk and five were in high risk. Although standard risk patients were more common in the group of pre-B1, this was not significant. Our results confirm the previous reports indicating heterogeneity of ALL. Immunophenotyping is not the only diagnostic test of importance, while morphological assessment still can be used in the diagnosis and classification of the disease.

  20. Improved Prognosis for Older Adolescents With Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Pui, Ching-Hon; Pei, Deqing; Campana, Dario; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Metzger, Monika L.; Bhojwani, Deepa; Inaba, Hiroto; Raimondi, Susana C.; Onciu, Mihaela; Howard, Scott C.; Leung, Wing; Downing, James R.; Evans, William E.; Relling, Mary V.

    2011-01-01

    Purpose The prognosis for older adolescents and young adults with acute lymphoblastic leukemia (ALL) has been historically much worse than that for younger patients. We reviewed the outcome of older adolescents (age 15 to 18 years) treated in four consecutive Total Therapy studies to determine if recent improved treatment extended to this high-risk group. Patients and Methods Between 1991 and 2007, 963 pediatric patients, including 89 older adolescents, were enrolled on Total Therapy studies XIIIA, XIIIB, XIV, and XV. In the first three studies, treatment selection was based on presenting clinical features and leukemic cell genetics. In study XV, the level of residual disease was used to guide treatment, which featured intensive methotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therapy for higher-risk ALL. Results The 89 older adolescents were significantly more likely to have T-cell ALL, the t(4;11)(MLL-AF4), and detectable minimal residual disease during or at the end of remission induction; they were less likely to have the t(12;21)(ETV6-RUNX1) compared with younger patients. In the first three studies, the 44 older adolescents had significantly poorer event-free survival and overall survival than the 403 younger patients. This gap in prognosis was abolished in study XV: event-free survival rates at 5 years were 86.4% ± 5.2% (standard error) for the 45 older adolescents and 87.4% ± 1.7% for the 453 younger patients; overall survival rates were 87.9% ± 5.1% versus 94.1% ± 1.2%, respectively. Conclusion Most older adolescents with ALL can be cured with risk-adjusted intensive chemotherapy without stem-cell transplantation. PMID:21172890

  1. Single-Cell Dynamic Analysis of Mitosis in Haploid Embryonic Stem Cells Shows the Prolonged Metaphase and Its Association with Self-diploidization

    Directory of Open Access Journals (Sweden)

    Ao Guo

    2017-05-01

    Full Text Available The recent establishment of mammalian haploid embryonic stem cells (ESCs provides new possibilities for genetic screening and for understanding genome evolution and function. However, the dynamics of mitosis in haploid ESCs is still unclear. Here, we report that the duration of mitosis in haploid ESCs, especially the metaphase, is significantly longer than that in diploid ESCs. Delaying mitosis by chemicals increased self-diploidization of haploid ESCs, while shortening mitosis stabilized haploid ESCs. Taken together, our study suggests that the delayed mitosis of haploid ESCs is associated with self-diploidization.

  2. Acute kidney injury and bilateral symmetrical enlargement of the kidneys as first presentation of B-cell lymphoblastic lymphoma.

    Science.gov (United States)

    Shi, Su-fang; Zhou, Fu-de; Zou, Wan-zhong; Wang, Hai-yan

    2012-12-01

    Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.

  3. Cremophor EL stimulates mitotic recombination in uvsH//uvsH diploid strain of Aspergillus nidulans

    Directory of Open Access Journals (Sweden)

    Cleverson Busso

    2004-03-01

    Full Text Available Cremophor EL is a solubilizer and emulsifier agent used in the pharmaceutical and foodstuff industries. The solvent is the principal constituent of paclitaxel's clinical formulation vehicle. Since mitotic recombination plays a crucial role in multistep carcinogenesis, the study of the recombinagenic potential of chemical compounds is of the utmost importance. In our research genotoxicity of cremophor EL has been studied by using an uvsH//uvsH diploid strain of Aspergillus nidulans. Since it spends a great part of its cell cycle in the G2period, this fungus is a special screening system for the study of mitotic recombination induced by chemical substances. Homozygotization Indexes (HI for paba and bi markers from heterozygous B211//A837 diploid strain were determined for the evaluation of the recombinagenic effect of cremophor EL. It has been shown that cremophor EL induces increase in mitotic crossing-over events at nontoxic concentrations (0.05 and 0.075% v/v.Cremofor EL (CEL é um solubilizante e emulsificante amplamente utilizado nas indústrias farmacêuticas e de gêneros alimentícios. É o principal veículo empregado nas formulações clínicas do antineoplásico paclitaxel. Considerando-se que a recombinação mitótica desempenha importante função no processo de carcinogênese, o estudo de substâncias químicas com potencial recombinagênico assume importância crucial, no sentido de se detectar aquelas que eventualmente possam atuar como promotoras de neoplasias. A genotoxicidade do cremofor EL foi estudada no presente trabalho, utilizando-se uma linhagem diplóide uvsH//uvsH de Aspergillus nidulans. Neste fungo as células vegetativas comumente repousam no período G2 do ciclo celular, facilitando a ocorrência da recombinação mitótica. O efeito recombinagênico do CEL foi avaliado através da determinação dos Índices de Homozigotização para os marcadores nutricionais paba e bi do diplóide heterozigoto B211//A837. Os

  4. Coexistence of diploid, triploid and tetraploid crucian carp (Carassius auratus in natural waters

    Directory of Open Access Journals (Sweden)

    You Cuiping

    2011-01-01

    Full Text Available Abstract Background Crucian carp (abbreviated CC belongs to the genus of Carassius within the family of Cyprinidae. It has been one of the most important freshwater species for Chinese aquaculture and is especially abundant in the Dongting water system of Hunan province. CC used to be considered as all diploid forms. However, coexistence of diploid (abbreviated 2nCC, triploid (abbreviated 3nCC and tetraploid crucian carp (abbreviated 4nCC population of the Dongting water system was first found by our recently researches. Results We examined the ploidy level and compared biological characteristics in different ploidy CC. In reproductive mode, 2nCC was bisexual generative and 4nCC generated all-female offspring by gynogenesis. However, 3nCC generated progenies in two different ways. 3nCC produced bisexual triploid offspring fertilized with 3nCC spermatozoa, while it produced all-female triploid offspring by gynogenesis when its ova were activated by heterogenous spermatozoa. The complete mitochondrial DNA of three different ploidy fishes was sequenced and analyzed, suggesting no significant differences. Interestingly, microchromosomes were found only in 3nCC, which were concluded to be the result of hybridization. Allogenetic DNA fragments of Sox genes were obtained in 3nCC and 4nCC, which were absent in 2nCC. Phylogenetics analysis based on Sox4 gene indicated 3nCC and 4nCC formed a separate group from 2nCC. Conclusions In summary, this is the first report of the co-existence of three types of different ploidy crucian carps in natural waters in China. It was proved that the coexistence of different ploidy CC was reproductively maintained. We further hypothesized that 3nCC and 4nCC were allopolyploids that resulted from hybridization. The different ploidy CC population we obtained in this study possesses great significance for the study of polyploidization and the evolution of vertebrates.

  5. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

    DEFF Research Database (Denmark)

    Andersson, Anna K; Ma, Jing; Wang, Jianmin

    2015-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older childr...

  6. Acute lymphoblastic leukaemia after treatment of nephrotic syndrome with immunosuppressive drugs.

    Science.gov (United States)

    Kuis, W; de Kraker, J; Kuijten, R H; Donckerwolcke, R A; Voûte, P A

    1976-06-01

    The authors present a 4-year-old girl with nephrotic syndrome who developed actue lymphoblastic leukaemia 5 months after the start of a combined treatment of alternate day prednisone and daily cyclophosphamide during 3 months. The nephrotic syndrome was due to focal segmental glomerulosclerosis. The occurrence of leukaemia might be related to the preceeding treatment with cyclophosphamide.

  7. Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute lymphoblastic leukemia and healthy controls.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Bierings, M.B.; Hoogerbrugge, P.M.; Ven, P.M. van de; Heijnen, C.J.; Kaspers, G.J.L.

    2012-01-01

    Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypoth

  8. Fatal Aspergillus rhinosinusitis during induction chemotherapy in a child with acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Flier, M. van der; Borgstein, J.A.; Lequin, M.H.; Sluis, I.M. van der

    2009-01-01

    Invasive fungal infections are a major problem in patients treated for hematologic malignancies. We report a 3-year-old girl who suffered from febrile neutropenia during induction therapy for acute lymphoblastic leukemia. Initial chest computed tomography revealed no evidence of intrapulmonary funga

  9. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the red

  10. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in pregnancy.

    Science.gov (United States)

    Mainor, Candace B; Duffy, Alison P; Atkins, Kristin L; Kimball, Amy S; Baer, Maria R

    2016-04-01

    BCR-ABL inhibitors administered in conjunction with chemotherapy have significantly improved outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia but, for patients diagnosed during pregnancy, data on risks to the fetus are limited. We report a woman treated with chemotherapy and imatinib mesylate who delivered a healthy baby at 30 weeks, and we discuss available data.

  11. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

  12. Apoptosis induction by Maackia amurensis agglutinin in childhood acute lymphoblastic leukemic cells

    DEFF Research Database (Denmark)

    Kapoor, Sarika; Marwaha, Ram; Majumdar, Siddhartha;

    2007-01-01

    Malignant transformation is known to be associated with changes in cell surface carbohydrate-architecture, which can be detected by lectins. In the present study, Maackia amurensis agglutinin (MAA), specific for NeuNAcalpha(2-->3)Gal/GalNAc showed strong binding with lymphoblasts of children havi...

  13. Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

    Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

  14. Analysis of handwriting of children during treatment for acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Reinders-Messelink, H.A.; Schoemaker, M.M.; Göeken, L.N.H.; Bökkerink, J.P.M.; Kamps, W.A.

    2001-01-01

    Background. Children treated for acute lymphoblastic leukemia (ALL) often complain about handwriting problems. Procedure. Using a computerized writing task, we have prospectively studied the processes necessary for the production of handwriting movements in I I children (5-12 years old) during treat

  15. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about the

  16. Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

    DEFF Research Database (Denmark)

    Lundin, Catarina; Forestier, Erik; Klarskov Andersen, Mette

    2014-01-01

    BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. METHODS...

  17. High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome

    DEFF Research Database (Denmark)

    Lundin, Catarina; Hjorth, Lars; Behrendtz, Mikael

    2012-01-01

    Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS...

  18. Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Bohnstedt, C; Levinsen, M; Rosthøj, S

    2013-01-01

    Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the Nordic Society of Pediatric Hematology...

  19. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment

    NARCIS (Netherlands)

    A. Holleman (Amy); C. Cheng (Cheng); C.H. Pui (Ching-Hon); W.E. Evans (William); M.V. Relling (Mary); R. Pieters (Rob); G.E. Janka-Schaub (Gritta); M.H. Cheok (Meyling); M.L. den Boer (Monique); W. Yang; A.J. Veerman; K.M. Kazemier (Karin); D. Pei (Deqing)

    2004-01-01

    textabstractBACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is curable with chemotherapy in approximately 80 percent of patients. However, the cause of treatment failure in the remaining 20 percent of patients is largely unknown. METHODS: We tested leukemia cells from 173

  20. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vaitkeviciene, Goda; Forestier, Erik; Hellebostad, Marit;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1-15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

  1. Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Loennerholm, Gudmar; Frost, Britt-Marie; Abrahamsson, Jonas; Behrendtz, Mikael; Castor, Anders; Forestier, Erik; Heyman, Mats; Uges, Donald R. A.; de Graaf, Siebold S. N.

    2008-01-01

    Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We he

  2. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about the

  3. Erroneous exchange of asparaginase forms in the treatment of acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Cheung, K.C.; Bemt, P.M. van den; Torringa, M.L.; Tamminga, R.Y.; Pieters, R.; Smet, P.A. de

    2011-01-01

    For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms wi

  4. Erroneous Exchange of Asparaginase Forms in the Treatment of Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Cheung, Ka-Chun; van den Bemt, Patricia M. L. A.; Torringa, Maarten L. J.; Tamminga, Rienk Y. J.; Pieters, Rob; de Smet, Peter A. G. M.

    2011-01-01

    For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms wi

  5. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Denys, B.; van der Sluijs-Gelling, A. J.; Homburg, C.; van der Schoot, C. E.; de Haas, V.; Philippe, J.; Pieters, R.; van Dongen, J. J. M.; van der Velden, V. H. J.

    2013-01-01

    Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are ob

  6. LONGITUDINAL-STUDY OF BONE-AGE IN ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    TAMMINGA, RYJ; ZWEENS, M; KAMPS, W; DRAYER, N

    1993-01-01

    Bone age was assessed in children with acute lymphoblastic leukaemia (ALL) using the Tanner-Whitehouse II method. X-rays of the left hand (wrist) were made at diagnosis and annually until 5 years after diagnosis. A total of 164 X-rays from 40 patients was available. During treatment bone age develop

  7. The significance of change of Th22 cells in patients with acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    刘立民

    2013-01-01

    Objective To investigate the proportion of Th22 cells in peripheral blood of patients with acute lympho-blastic leukemia(ALL) and evaluate its significance.Methods The proportions of Th22 cells in peripheral blood of B-ALL and T-ALL patients before therapy(group 1),

  8. Acute lymphoblastic leukemia and obesity : increased energy intake or decreased physical activity?

    NARCIS (Netherlands)

    Jansen, H.; Postma, A.; Stolk, R. P.; Kamps, W. A.

    2009-01-01

    Background Obesity is a well-known problem in children with acute lymphoblastic leukemia ( ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with inter

  9. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Shah, S.; Schrader, K.A.; Waanders, E.; Timms, A.E.; Vijai, J.; Miething, C.; Wechsler, J.; Yang, J.; Hayes, J.; Klein, R.J.; Zhang, Jinghui; Wei, L.; Wu, G.; Rusch, M.; Nagahawatte, P.; Ma, J; Chen, S.C.; Song, G.; Cheng, J.; Meyers, P.; Bhojwani, D.; Jhanwar, S.; Maslak, P.; Fleisher, M.; Littman, J.; Offit, L.; Rau-Murthy, R.; Fleischut, M.H.; Corines, M.; Murali, R.; Gao, X.; Manschreck, C.; Kitzing, T.; Murty, V.V.; Raimondi, S.C.; Kuiper, R.P.; Simons, A.; Schiffman, J.D.; Onel, K.; Plon, S.E.; Wheeler, D.A.; Ritter, D.; Ziegler, D.S.; Tucker, K.; Sutton, R.; Chenevix-Trench, G.; Li, J.; Huntsman, D.G.; Hansford, S.; Senz, J.; Walsh, T.; Lee, M. van der; Hahn, C.N.; Roberts, K.G.; King, M.C.; Lo, S.M.; Levine, R.L.; Viale, A.; Socci, N.D.; Nathanson, K.L.; Scott, H.S.; Daly, M.; Lipkin, S.M.; Lowe, S.W.; Downing, J.R.; Altshuler, D.; Sandlund, J.T.; Horwitz, M.S.; Mullighan, C.G.; Offit, K.

    2013-01-01

    Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly1

  10. Unravelling Pathobiological Molecular Mechanisms of T-Cell Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    R.D. Mendes (Rui Daniel)

    2016-01-01

    markdownabstractT-cell acute lymphoblastic leukemia (T-ALL) represents 10-15% of pediatric acute leukemias. Despite major therapeutic improvements due to treatment intensification and refined risk-adapted stratification during the past decade, ~30% of T-ALL cases relapse with very poor prognosis.

  11. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R. Pieters (Rob); E.-J.D. Wind (Ernst-Jan); J.H.J.M. Bessems (Gert); M.M. van den Heuvel-Eibrink (Marry)

    2014-01-01

    textabstractThere is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery,

  12. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. Th

  13. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse.

  14. Prognosis in childhood and adult acute lymphoblastic leukaemia : a question of maturation?

    NARCIS (Netherlands)

    Plasschaert, SLA; Kamps, WA; Vellenga, E; de Vries, EGE; de Bont, ESJM

    2004-01-01

    Acute lymphoblastic leukaemia (ALL) is a disease diagnosed in children as well as adults. Progress in the treatment of ALL has led to better survival rates, however, children have benefited more from improved treatment modalities than adults. Recent evidence has underscored that the difference in ch

  15. Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Plasschaert, SLA; de Bont, ESJM; Boezen, M; vander Kolk, DM; Daenen, SMJG; Faber, KN; Kamps, WA; de Vries, EGE; Vellenga, E

    2005-01-01

    PURPOSE: Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the exp

  16. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    D. Schotte (Diana); R.X. de Menezes (Renee); F. Akbari Moqadam (Farhad); L.M. Khankahdani (Leila Mohammadi); E.A.M. Lange-Turenhout (Ellen); C. Chen (Caifu); R. Pieters (Rob); M.L. den Boer (Monique)

    2011-01-01

    textabstractBackground MicroRNA regulate the activity of protein-coding genes including those involved in hematopoietic cancers. The aim of the current study was to explore which microRNA are unique for seven different subtypes of pediatric acute lymphoblastic leukemia. Design and Methods Expression

  17. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation

    NARCIS (Netherlands)

    I. Lauw (Ivoune); B. van der Holt (Bronno); S. Middeldorp (Saskia); J.C.M. Meijers; J.J. Cornelissen (Jan); B.J. Biemond (Bart)

    2013-01-01

    textabstractTreatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, particularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle

  18. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours

  19. Neuropsychological outcome in chemotherapy-only-treated children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Jansen, Nathalie C. A. J.; Kingma, Annette; Schuitema, Arnout; Bouma, Anke; Veerman, Anjo J. P.; Kamps, Willem A.

    2008-01-01

    Purpose To evaluate neuropsychological functioning over time in children treated for acute lymphoblastic leukemia (ALL) with chemotherapy only. Patients and Methods Forty-nine consecutive patients (median age at first assessment, 6.8 years; range, 4.0 to 11.8 years) treated with intrathecal and syst

  20. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. Th

  1. Glioblastoma multiforme in a child with acute lymphoblastic leukemia: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Shah Kirit

    2004-07-01

    Full Text Available An 11-year-old boy with acute lymphoblastic leukemia had received prophylactic cranial irradiation (1800 cGy /10 fractions and intrathecal methotrexate. Five years later, he developed a glioblastoma multiforme in the right frontal region while the leukemia was in remission. It is possible that the glioma may have been induced by radiation and /or chemotherapy.

  2. Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R.D. van Beek (Robert Diederik); S.M.P.F. de Muinck Keizer-Schrama (Sabine); A.G. Uitterlinden (André); W.C.J. Hop (Wim); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2010-01-01

    textabstractBackground This study investigates pharmacogenetic risk factors for bone mineral (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic leukemia Design and Methods We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2

  3. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia.

    Science.gov (United States)

    Te Winkel, Mariël L; Pieters, Rob; Wind, Ernst-Jan D; Bessems, J H J M Gert; van den Heuvel-Eibrink, Marry M

    2014-03-01

    There is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bisphosphonates, 6 hydroxymethyl-glutaryl CoA reductase inhibitors, anticoagulants and hyperbaric oxygen, and terms related to these MESH terms. A randomized controlled trial showed that osteonecrosis can be prevented by intermittent, instead of continuous, corticosteroid administration. The studies on interventions after onset of osteonecrosis were of low-quality evidence. Seven pediatric acute lymphoblastic leukemia studies described non-surgical interventions; bisphosphonates (n=5), hyperbaric oxygen therapy (n=1), or prostacyclin analogs (n=1). Safety and efficacy studies are lacking. Five studies focused on surgical interventions; none was of sufficient quality to draw definite conclusions. In conclusion, preventing osteonecrosis is feasible in a proportion of the pediatric acute lymphoblastic leukemia patients by discontinuous, instead of continuous, steroid scheduling. The questions as to how to treat childhood acute lymphoblastic leukemia patients with osteonecrosis cannot be answered as good-quality studies are lacking.

  4. Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, Marissa A. H.; Pluijm, Saskia M. F.; te Winkel, Mariel L.; de Groot-Kruseman, Hester A.; Fiocco, Martha; Hoogerbrugge, Peter; Leeuw, Jan; Bruin, Marrie C. A.; van der Sluis, Inge M.; Bresters, Dorien; Lequin, Maarten H.; Roos, Jan C.; Veerman, Anjo J. P.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2015-01-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence e

  5. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R. Pieters (Rob); E.-J.D. Wind (Ernst-Jan); J.H.J.M. Bessems (Gert); M.M. van den Heuvel-Eibrink (Marry)

    2014-01-01

    textabstractThere is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bis

  6. Free Air Intraperitoneally During Chemotherapy for Acute Lymphoblastic Leukemia : Consider Pneumatosis Cystoides Intestinalis

    NARCIS (Netherlands)

    Groninger, Ellis; Hulscher, Jan B. F.; Timmer, Bert; Tamminga, Rienk Y. J.; Broens, Paul M. A.

    2010-01-01

    Intraperitoneal free air in a child with acute lymphoblastic leukemia (ALL) treated with induction chemotherapy is an ominous sign suspective of gastrointestinal perforation. We report a case of pneumatosis cystoides intestinalis (PCI) with free intraperitoneal air without bowel perforation in a chi

  7. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

  8. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia

    NARCIS (Netherlands)

    von Bergh, ARM; Beverloo, HB; Rombout, P; van Wering, ER; van Weel, MH; Beverstock, GC; Kluin, PM; Slater, RM; Schuuring, E

    2002-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2; 11)(p 15;p 14) and an MLL rearrangement on Southern blot analysis, Rapid amplification of cDNA ends-polymerase chain react

  9. Minimal residual disease diagnostics in acute lymphoblastic leukemia: Need for sensitive, fast, and standardized technologies

    NARCIS (Netherlands)

    J.J.M. van Dongen (Jacques); V.H.J. van der Velden (Vincent); M. Brüggemann (Monika); A. Orfao (Alberto)

    2015-01-01

    textabstractMonitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group

  10. LONGITUDINAL-STUDY OF BONE-AGE IN ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    TAMMINGA, RYJ; ZWEENS, M; KAMPS, W; DRAYER, N

    1993-01-01

    Bone age was assessed in children with acute lymphoblastic leukaemia (ALL) using the Tanner-Whitehouse II method. X-rays of the left hand (wrist) were made at diagnosis and annually until 5 years after diagnosis. A total of 164 X-rays from 40 patients was available. During treatment bone age

  11. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours o

  12. Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Juncker, Agnieszka; Schmiegelow, K.

    2004-01-01

    Gene expression profiling is a promising tool for classification of pediatric acute lymphoblastic leukemia ( ALL). We analyzed the gene expression at the time of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free survival or relapse after treatment by NOPHO-ALL92 or 2000...

  13. Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

    2016-01-01

    PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree...

  14. Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Bergmann, Kristin; Hasle, Henrik; Asdahl, Peter

    2016-01-01

    The purpose of the study was to assess the risk of firsttime bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL...

  15. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L.; Wehner, Peder S.

    2017-01-01

    with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C...

  16. Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Carlsen, Niels L T; Oxhøj, Henrik

    2007-01-01

    At present about 80% of children with acute lymphoblastic leukemia (ALL) will be cured following treatment with multi-drug chemotherapy. A major concern for this growing number of survivors is the risk of late effects of treatment. The aim of this study was to determine whether signs...

  17. Free Air Intraperitoneally During Chemotherapy for Acute Lymphoblastic Leukemia : Consider Pneumatosis Cystoides Intestinalis

    NARCIS (Netherlands)

    Groninger, Ellis; Hulscher, Jan B. F.; Timmer, Bert; Tamminga, Rienk Y. J.; Broens, Paul M. A.

    Intraperitoneal free air in a child with acute lymphoblastic leukemia (ALL) treated with induction chemotherapy is an ominous sign suspective of gastrointestinal perforation. We report a case of pneumatosis cystoides intestinalis (PCI) with free intraperitoneal air without bowel perforation in a

  18. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nordlund, Jessica; Bäcklin, Christofer L; Wahlberg, Per

    2013-01-01

    BACKGROUND: Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic...

  19. Fine motor and handwriting problems after treatment for childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    ReindersMesselink, HA; Schoemaker, MM; Hofte, M; Goeken, LNH; Kingma, A; vandenBriel, MM; Kamps, WA

    1996-01-01

    Motor skills were investigated in 18 children 2 years after treatment for acute lymphoblastic leukemia (ALL). Cross and fine motor functioning were examined with the Movement Assessment Battery for Children. Handwriting as a specific fine motor skill was studied with a computerized writing task. We

  20. Serial Ultrasound Monitoring for Early Recognition of Asparaginase Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, K.; Henriksen, Birthe Merete

    2015-01-01

    BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L...