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Sample records for childhood leukaemia fallon

  1. Nuclear power and childhood leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Grimston, M. (AEA Technology, London (UK))

    1991-06-19

    The possibility of illness caused by exposure to emissions from nuclear power plants continues to raise enormous public concern. Nowhere is this more evident than in the debate over the aetiology of childhood leukaemias. This review explores the evidence in relation to this and other diseases which are linked in the public's mind to nuclear power. The scientific evidence presented suggests that these links are more tenuous than is commonly believed. (author).

  2. Causes of childhood leukaemia and lymphoma

    International Nuclear Information System (INIS)

    Childhood cancer is rare comprising less than 1% of all malignancies diagnosed each year in developed countries. Leukaemia is the commonest form of cancer in children accounting for around a third of all childhood cancer, with acute lymphoblastic leukaemia (ALL) being the most prevalent. Biologically specific subtypes of ALL and acute myeloblastic leukaemia (AML), the other major morphological type of childhood leukaemia, are characterised by chromosomal changes. Whilst over 200 genes have been associated with chromosomal translocations, to date, only MLL, TEL, and AML1 have been linked with childhood leukaemia. Interestingly, there is increasing evidence to support the theory that gene rearrangements such as these may originate in utero. As with many other human diseases, both genetic and environmental factors have been implicated in the aetiology of the disease. Although much has been documented with regard to diet, smoking, alcohol consumption and recreational and prescription drug use during pregnancy, there is no consistent evidence to support a link with any of these factors and childhood leukaemia. However, findings from studies investigating prenatal and early life exposures are often based on small numbers of cases as both the type of cancer and exposure are rare. Furthermore, accurate information relating to past exposures can be difficult to obtain and is often reliant on self-reporting. To further our understanding of the aetiology of childhood leukaemia and lymphoma, there are areas which clearly warrant investigation. These include collection of parental dietary folate data combined with genetic analysis of the folate related genes, in utero exposure to DNA topoisomerase II inhibitors, and the possible effects of assisted reproduction technology on disease susceptibility

  3. Residential exposures to pesticides and childhood leukaemia

    OpenAIRE

    Metayer, Catherine; Buffler, Patricia A.

    2008-01-01

    Like many chemicals, carcinogenicity of pesticides is poorly characterised in humans, especially in children, so that the present knowledge about childhood leukaemia risk derives primarily from epidemiological studies. Overall, case–control studies published in the last decade have reported positive associations with home use of insecticides, mostly before the child's birth, while findings for herbicides are mixed. Previous studies relied solely on self-reports, therefore lacking information ...

  4. Maternal and birth characteristics in relation to childhood leukaemia.

    Science.gov (United States)

    Podvin, Danise; Kuehn, Carrie M; Mueller, Beth A; Williams, Michelle

    2006-07-01

    Our objective was to investigate the association of childhood leukaemia with selected maternal and birth characteristics by conducting a population-based case-control study using linked cancer registry and birth certificate records for Washington State. We compared maternal and infant characteristics of 595 Washington-born residents neonatal jaundice (OR 1.5; 95% CI 1.1, 2.1), and Down's syndrome (OR 31.3; 95% CI 6.4, 153.4) were associated with an increased risk of leukaemia. Among women with 2+ pregnancies, having at least two prior early (knowledge of inherent and possibly prenatal influences on the occurrence of this disease. PMID:16879503

  5. Childhood leukaemia around Canadian nuclear facilities. Phase 2

    International Nuclear Information System (INIS)

    Prompted by findings of increased occurrence of childhood leukaemia in the vicinity of some nuclear facilities in the United Kingdom, this study aimed to investigate whether the frequency of leukaemia among children born to mothers living near nuclear facilities in Ontario differed from the provincial average. The Ontario Cancer Registry was used to identify 1894 children aged 0 to 14 years who died from leukaemia between 1950 and 1987, and 1814 children who were diagnosed with leukaemia between 1964 and 1986. Residence at birth and death was obtained from birth and death certificates. Analyses were performed separately for nuclear research and development facilities; uranium mining, milling and refining facilities; and, nuclear generating stations; and for areas within the same county as the facility and 'nearby' - within a 25-km radius of the facility. Risk estimates were calculated as the ratio of the observed (O) number of events over the expected (E) number. In the vicinity of nuclear research and development facilities the rate of leukaemia was less than expected and within the bound of chance variation. In the areas around the uranium mining, milling and refining facilities and nuclear power plants leukaemia occurred slightly more frequently than expected, but due to small frequencies these differences may have arisen due to chance. Large differences between observed and expected rates were not detected around any of the Ontario facilities. This study was large enough to detect excess risks of the magnitude reported in the United Kingdom, but it was not large enough to discriminate between the observed relative risks and a chance finding. Levels of leukaemia detected near nuclear generating stations indicate the need for further investigation. (20 tabs., 15 figs., 32 refs.)

  6. Leukaemia clusters in childhood: geographical analysis in Britain

    Energy Technology Data Exchange (ETDEWEB)

    Knox, E.G.

    1994-08-01

    Study objective - To validate previously demonstrated spatial clustering of childhood leukaemias by showing relative proximities of selected map features to cluster locations, compared with control locations. If clusters are real, then they are likely to be close to a determining hazard. Design -Cluster postcode loci and partially matched control postcodes were compared in terms of distances to railways, main roads, churches, surface water, woodland areas, and railside industrial installations. Further supporting comparisons between non-clustered cases and random postcode controls with those map features representable as single grid points were made. Setting -England, Wales, and Scotland 1966-83. Subjects - Grid referenced registrations of 9406 childhood leukaemias and non-Hodgkin`s lymphomas, including 264 pairs (or more) separated by <150 m, and grid references of random postcodes in equal numbers. Main results - the 264 clusters showed relative proximities (or the inverse) to several map features, of which the most powerful was an association with railways. The non-railway associations seemed to be statistically indirect. Some railside industrial installations, identified from a railway atlas, also showed relative proximities to leukaemia clusters, as well as to non-clustered cases, but did not ``explain`` the railway effect. These installations, with seemingly independent geographical associations, included oil refineries, petrochemical plants, oil storage and oil distribution depots, power stations, and steelworks. Conclusions - The previously shown childhood leukaemia clusters are confirmed to be non-random through their systematic associations with certain map features when compared with the control locations. The common patterns of close association of clustered and non-clustered cases imply a common aetiological component arising from a common environmental hazard - namely the use of fossil fuels, especially petroleum. (UK)

  7. What Role for Angiogenesis in Childhood Acute Lymphoblastic Leukaemia?

    Directory of Open Access Journals (Sweden)

    P. Schneider

    2011-01-01

    Full Text Available The role of angiogenesis in acute leukaemia has been discussed since the cloning of the gene of vascular endothelial growth factor (VEGF from the acute myelogenous leukemia cell line (HL60 and, thereafter, when the first studies reported increased bone marrow vascularity and elevation of angiogenic cytokines in acute lymphoblastic leukaemia (ALL. VEGF and basic fibroblast growth factor (bFGF are the major proangiogenic cytokines that have been studied, and evaluation of their prognostic impact in childhood ALL has been reported in several studies, though with controversial results. The antiangiogenic response, contributing to the angiogenic balance, has scarcely been reported. The origin of the factors, their prognostic value, and their relevance as good markers of what really happens in the bone marrow are discussed in this paper. The place of antiangiogenic drugs in ALL has to be defined in the global treatment strategy.

  8. Survival in France after childhood acute leukaemia and non-Hodgkin's lymphoma (1990-2000).

    OpenAIRE

    Goubin, Aurélie; Auclerc, Marie-Françoise; Auvrignon, Anne; Patte, Catherine; Bergeron, Christophe; Hémon, Denis; Clavel, Jacqueline

    2006-01-01

    This article describes the survival after childhood acute leukaemia (AL) and non-Hodgkin's lymphoma (NHL) of French population aged less than 15 years. The French National Registry of Childhood Leukaemia and Lymphoma recorded 3995 cases of acute lymphoblastic leukaemia (ALL), 812 of acute myeloid leukaemia (AML) and 1137 of NHL over the period from 1990 to 2000. Overall survival rates at 5 years were 82% (95% CI 80-83), 58% (95% CI 54-61) and 87% (95% CI 85-89) for ALL, AML and NHL, respectiv...

  9. Overview of recent studies on childhood leukaemia, intra-uterine growth and diet

    International Nuclear Information System (INIS)

    Many studies have looked at the association between birth weight and risk of acute lymphoblastic leukaemia in children, but few have been able to examine the growth by incorporating estimates of gestational age. Recent results suggest that increased growth is associated with increased risk of childhood leukaemia. Evidence is also gathering that certain dietary intakes, possibly folate, in mothers, are also related to leukaemia occurrence. If these associations are real, they may be operating through growth factor pathways. (authors)

  10. IRSN-ANCCLI partnership. Information day: Childhood leukaemia around French nuclear power plants - April 2012

    International Nuclear Information System (INIS)

    As an epidemiological study performed by the INSERM highlighted an excess of childhood leukaemia within 5 km around nuclear power plants during the 2002-2007 period, this meeting has been organised to discuss this issue. After a presentation of these results, a contribution discusses the context and research perspectives on the relationship between childhood leukaemia and nuclear sites. After the reported debate, a contribution presents the conclusion of a work-group on childhood leukaemia and ASN works, and a last one presents the activities of a work-group gathering the ANCCLI, IRSN and InVS on the health impact of nuclear installations. A debate on these issues is reported

  11. Seasonal variations in the onset of childhood leukaemia and lymphoma.

    OpenAIRE

    Westerbeek, R. M.; Blair, V; Eden, O B; Kelsey, A M; Stevens, R. F.; Will, A. M.; Taylor, G M; Birch, J M

    1998-01-01

    Infection has long been suspected as a possible factor in the aetiology of leukaemia and lymphoma. If seasonal variation in the onset of disease could be shown in any of the diagnostic subgroups of leukaemia or lymphoma, this would provide supportive evidence of an aetiology linked to exposure to infection. All cases in the Manchester Children's Tumour Registry (aged 0-14 years at diagnosis) with acute lymphoblastic leukaemia (ALL), acute non-lymphocytic leukaemia (ANLL), Hodgkin's disease (H...

  12. The UK Childhood Cancer Study: Maternal occupational exposures and childhood leukaemia and lymphoma

    International Nuclear Information System (INIS)

    Risks of childhood leukaemia and lymphoma were investigated for specific work-related exposures of mothers in the UK Childhood Cancer Study. Interviews with parents of 1881 leukaemia and lymphoma cases (0-14 years) and 3742 controls collected job histories recording exposure to eight specific agents. Exposure was (1) self-reported and (2) reviewed, based mainly on exposure probability and exposure level. Completeness, consistency and sufficiency evaluated data quality. Of all job exposures which were self-reported as exposed, 33% cases and 34% controls remained classified as exposed after review, with the remainder designated as partially exposed or unexposed. No review of underreporting of exposure was made. Data quality was 'good' for 26% of cases and 24% of controls. For self-reported exposure, significant risks of acute lymphoblastic leukaemia (ALL) were observed for solvents and petrol in all time windows. For reviewed exposure, solvents remained significant for ALL during pregnancy and post-natality. Restricting analyses to good-quality information removed all significant results. Refinement of exposure assessment revealed misclassification of self-reported exposures and data quality influenced risk assessment. Maternal exposure to solvents should further be investigated. These findings must invoke caution in the interpretation of risks reliant on self-reported occupational data. (authors)

  13. Somatic PTPN11 mutations in childhood acute myeloid leukaemia.

    Science.gov (United States)

    Tartaglia, Marco; Martinelli, Simone; Iavarone, Ivano; Cazzaniga, Giovanni; Spinelli, Monica; Giarin, Emanuela; Petrangeli, Valentina; Carta, Claudio; Masetti, Riccardo; Aricò, Maurizio; Locatelli, Franco; Basso, Giuseppe; Sorcini, Mariella; Pession, Andrea; Biondi, Andrea

    2005-05-01

    Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4.4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.

  14. Personalization of dexamethasone therapy in childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jackson, Rosanna K; Irving, Julie A E; Veal, Gareth J

    2016-04-01

    Dexamethasone is a key component in the treatment of childhood acute lymphoblastic leukaemia (ALL). Despite playing a key role in the improved survival of ALL over several decades, intensification of dexamethasone therapy has also contributed to the increased toxicity associated with treatment, which is now seen to be at unacceptable levels given the favourable disease prognosis. Therefore the focus for treatment is now shifting towards reducing toxicity whilst maintaining current survival rates. As approximately 50% of patients were successfully treated on less intensive protocols of the 1980s, it has been questioned whether therapy intensification is necessary in all patients. Furthermore, there remains a subset of children who are still not cured of their disease. New strategies are therefore needed to identify patients who could benefit from dose reduction or intensification. However, adjusting a potentially life threatening therapy is a challenging task, particularly given the heterogeneous nature of ALL. This review focuses on the potential for patient stratification based on our current knowledge of dexamethasone pharmacokinetics, pharmacogenetics and the action of dexamethasone at the cellular level. A carefully designed, combined approach is needed if we are to achieve the aim of improved personalization of dexamethasone therapy for future patients. PMID:26729065

  15. Childhood leukaemia around Canadian nuclear facilities. Phase 1

    International Nuclear Information System (INIS)

    A ninefold excess risk of leukaemia, as observed in vicinity of the Sellafield facility, was not observed amongst children born to mothers residing in the areas around nuclear research facilities and uranium mining, milling and refining facilities in Ontario. In the vicinity of nuclear research facilities, the rate of leukaemia was, in fact, less than expected. In the areas around the uranium mining, milling and refining facilities; leukaemia occurred slightly more frequently than expected; however, due to small frequencies these results may have risen by chance. A slightly greater than expected occurrence of leukaemia was also detected, which may well have been due to chance, in an exploratory study of the areas around nuclear power generating stations in Ontario

  16. Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research

    International Nuclear Information System (INIS)

    Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out. (review)

  17. Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Lund, Bendik; Åsberg, Ann; Heyman, Mats;

    2011-01-01

    BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92 and...

  18. Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Lund, Bendik; Åsberg, Ann; Heyman, Mats;

    2011-01-01

    BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92 an...... towards patients at risk. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc....

  19. 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

    toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall......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...

  20. Trends in childhood leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing.

    OpenAIRE

    Darby, S. C.; Olsen, J. H.; Doll, R.; Thakrar, B.; Brown, P. D.; Storm, H H; Barlow, L.; Langmark, F.; Teppo, L; H. Tulinius

    1992-01-01

    OBJECTIVE--To obtain further information about the risks of childhood leukaemia after exposure to ionising radiation at low doses and low dose rates before or after birth or to the father's testes shortly before conception. DESIGN--Observational study of trends in incidence of childhood leukaemia in relation to estimated radiation exposures due to fallout from atmospheric nuclear weapons testing during the 1950s and 1960s. SETTING--Nordic countries. SUBJECTS--Children aged under 15 years. MAI...

  1. Quantifying the effect of population mixing on childhood leukaemia risk: the Seascale cluster

    OpenAIRE

    Dickinson, H O; Parker, L.

    1999-01-01

    A statistical model was developed based on Poisson regression of incidence of childhood leukaemia and non-Hodgkin’s lymphoma (NHL) in relation to population mixing among all 119 539 children born 1969–1989 to mothers living in Cumbria, north-west England, (excluding Seascale). This model was used to predict the number of cases in Seascale (the village adjacent to the Sellafield nuclear installation) children, born 1950–1989 and diagnosed before 1993. After allowing for age, the incidence of a...

  2. Childhood leukaemia and ordnance factories in west Cumbria during the Second World War

    OpenAIRE

    Kinlen, L

    2006-01-01

    Much evidence has accumulated that childhood leukaemia (CL) is a rare response to a common, but unidentified, infection and in particular that situations involving the unusual mixing of urban and rural groups (approximating to, respectively, groups infected with, and susceptible to, the relevant microorganism) can produce localised epidemics with consequent increases of the infrequent leukaemic complication. During the Second World War, explosives production factories were built and operated ...

  3. Scottish validation study of cancer registration data childhood leukaemia 1968-1981: Pt. 1

    International Nuclear Information System (INIS)

    This study attempted to validate central registration data on all childhood leukaemia cases in Scotland between 1968 and 1981 in line with the Black Enquiry concerning West Cumbria. Missing files precluded a complete verification, but minor errors of registration were found in 44% of cases. A small number of important mistakes of omission (eight cases), wrong diagnosis (six cases) and postal code errors (nine cases) were found which might affect epidemiological studies of these relatively rare diseases. Precise and verified prospective data collection at the time of diagnosis is essential if the spatial distribution of childhood cancers is being studied. (author)

  4. Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England.

    Science.gov (United States)

    McNally, Richard J Q; Alston, Robert D; Cairns, Donal P; Eden, Osborn B; Birch, Jillian M

    2003-10-01

    Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976-2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0-14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small-area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0.05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0.001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.

  5. Childhood leukaemia in North West England 1954-1977: epidemiology, incidence and survival.

    Science.gov (United States)

    Birch, J M; Swindell, R; Marsden, H B; Morris Jones, P H

    1981-03-01

    The annual incidence of leukaemia among children aged up to 14 years as estimated by the Manchester Children's Tumour Registry has been analysed for the 24 years 1954-1977. A significant increase in acute lymphoid leukaemia (ALL) was found, while the incidence of acute myeloid leukaemia (AML) remained constant. Other types of leukaemia were too rare to be analysed separately. The increase in ALL was concentrated among boys in the 1--5-year age group. Analysis with respect to initial white-cell count showed the increase to be more pronounced in children with initial white cell counts of 1-5 x 10(4)/microliters. The proportion of cases presenting in Lancashire compared with Greater Manchester did not change during the study period. The distribution of cases with respect to social class and socio-economic group of the parents also remained constant. Due to advances in the treatment of childhood ALL survival improved considerably during the study period and no increase in mortality was seen.

  6. Spatial variation of natural radiation and childhood leukaemia incidence in Great Britain

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, Sylvia; Monfort, Christine [Institut National de la Sante et de la Recherche Medicale, Villejuif, 94 (France); Green, Martyn; Muirhead, Colin [National Radiological Protection Board, Chilton (United Kingdom); Draper, Gerald [Oxford Univ., Childhood Cancer Research Group, Oxford (United Kingdom)

    1995-12-31

    This paper describes an analysis of the geographical variation of childhood leukaemia incidence in Great Britain over a 15 year period in relation to natural radiation (gamma and radon). Data at the level of the 459 district level local authorities in England, Wales and regional districts in Scotland are analysed in two complementary ways: first, by Poisson regressions with the inclusion of environmental covariates and a smooth spatial structure; secondly, by a hierarchical Bayesian model in which extra-Poisson variability is modelled explicitly in terms of spatial and non-spatial components. From this analysis, we deduce a strong indication that a main part of the variability is accounted for by a local neighbourhood `clustering` structure. This structure is furthermore relatively stable over the 15 year period for the lymphocytic leukaemias which make up the majority of observed cases. We found no evidence of a positive association of childhood leukaemia incidence with outdoor or indoor gamma radiation levels. There is no consistent evidence of any association with radon levels. Indeed, in the Poisson regressions, a significant positive association was only observed for one 5-year period, a result which is not compatible with a stable environmental effect. Moreover, this positive association became clearly non-significant when over-dispersion relative to the Poisson distribution was taken into account. (author).

  7. Childhood leukaemia and non-Hodgkin's lymphoma near large rural construction sites, with a comparison with Sellafield nuclear site.

    OpenAIRE

    Kinlen, L. J.; Dickson, M; Stiller, C A

    1995-01-01

    OBJECTIVE--To determine whether population mixing produced by large, non-nuclear construction projects in rural areas is associated with an increase in childhood leukaemia and non-Hodgkin's lymphoma. DESIGN--A study of the incidence of leukaemia and non-Hodgkin's lymphoma among children living near large construction projects in Britain since 1945, situated more than 20 km from a population centre, involving a workforce of more than 1000, and built over three or more calendar years. For perio...

  8. SETIL: Italian multicentric epidemiological case–control study on risk factors for childhood leukaemia, non hodgkin lymphoma and neuroblastoma: study population and prevalence of risk factors in Italy

    OpenAIRE

    Magnani, Corrado; Mattioli, Stefano; Miligi, Lucia; Ranucci, Alessandra; Rondelli, Roberto; Salvan, Alberto; Bisanti, Luigi; Masera, Giuseppe; Rizzari, Carmelo; Zambon, Paola; Cannizzaro, Santina; Gafà, Lorenzo; Luzzatto, Lia Lidia; Benvenuti, Alessandra; Michelozzi, Paola

    2014-01-01

    Background Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case–control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descript...

  9. Day-care, early common infections and childhood acute leukaemia: a multicentre French case–control study

    Science.gov (United States)

    Perrillat, F; Clavel, J; Auclerc, M F; Baruchel, A; Leverger, G; Nelken, B; Philippe, N; Schaison, G; Sommelet, D; Vilmer, E; Hémon, D

    2002-01-01

    We conducted a case–control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers. The interviews included questions on early common infections, day-care attendance, breast-feeding, birth order and infantile diseases. Odds ratios were estimated using an unconditional regression model including the stratification variables, parental socio-economic status and perinatal characteristics. Birth order was not associated with childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A statistically-significant inverse association was observed between childhood leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4–1.0)), repeated early common infections (⩾4 per year before age two, odds ratio=0.6 (0.4–1.0)), surgical procedures for ear–nose–throat infections before age two (odds ratio=0.5 (0.2–1.0)) and prolonged breast-feeding (⩾6 months, odds ratio=0.5 (0.2–1.0)). In the multivariate model including day-care attendance, early common infections and breast-feeding, results concerning breast-feeding remained unchanged. A statistically significant interaction between day-care attendance and repeated early common infections was observed. When the interaction was taken into account, the simple effects of day-care and early common infections disappeared (odds ratio=1.1 (0.5–2.3) and odds ratio=0.8 (0.5–1.3), respectively) while the joint effect of day-care attendance and early common infections was negatively associated with childhood leukaemia (odds ratio=0.3 (0.1–0.8)). All the above associations were observed both for acute lymphoblastic leukaemia and acute non

  10. Up-to-date monitoring of childhood cancer long-term survival in Europe: Leukaemias and lymphomas

    NARCIS (Netherlands)

    H. Brenner (Hermann); J.W.W. Coebergh (Jan Willem); D.M. Parkin; I. Izarzugaza; J. Clavel; V. Arndt (Volker); E. Steliarova-Foucher

    2007-01-01

    textabstractBackground: In recent decades, following the introduction of effective chemotherapy, the prognosis of children with leukaemia and lymphoma has dramatically improved, but data reflecting further possible improvement achieved in the 1990s are scarce. Methods: Using the Automated Childhood

  11. Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas;

    2015-01-01

    High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue...

  12. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region

    NARCIS (Netherlands)

    Pui, CH; Gaynon, PS; Boyett, JM; Chessells, JM; Baruchel, A; Kamps, W; Silverman, LB; Biondi, A; Harms, DO; Vilmer, E; Schrappe, M; Camitta, B

    2002-01-01

    Background The prognosis and optimum treatment of childhood acute lymphoblastic leukaemia (ALL) with abnormalities of chromosomal band 11q23 are controversial. We aimed to identify prognostic factors that might help in planning future therapy, and to assess the effectiveness of haemopoietic stem-cel

  13. DNA incorporation of 6-thioguanine nucleotides during maintenance therapy of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hedeland, Rikke L; Hvidt, Kristian; Nersting, Jacob;

    2010-01-01

    To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN......), methylated metabolites (E-MeMP), Methotrexate polyglutamates (E-MTX), and to thiopurine methyltransferase activity (TPMT)....

  14. TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells.

    Directory of Open Access Journals (Sweden)

    Robert J Weeks

    Full Text Available Childhood acute lymphoblastic leukaemia (ALL is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity.Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5'-aza-2'-deoxycytidine (decitabine exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays.In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity.These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL.

  15. 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......, Iceland, Norway and Sweden). Ten-year event-free (pEFS(10 y)) survival and overall (pOS(10 y)) survival were 0.75 ± 0.01 and 0.85 ± 0.01, respectively. Although treatment intensity was determined by WBC, non-remission and relapsed patients still had significantly higher WBC than those in remission for B-cell...

  16. The risk profile of childhood leukaemia in Greece: a nationwide case-control study.

    Science.gov (United States)

    Petridou, E; Trichopoulos, D; Kalapothaki, V; Pourtsidis, A; Kogevinas, M; Kalmanti, M; Koliouskas, D; Kosmidis, H; Panagiotou, J P; Piperopoulou, F; Tzortzatou, F

    1997-01-01

    The risk profile of childhood leukaemia in Greece was studied through a case-control investigation that included all 153 incident cases of the disease, ascertained throughout the country during 1993 and 1994, and two hospital controls for every case matched for gender, age and place of residence. The data were analysed using conditional logistic regression and the associations are expressed in terms of adjusted odds ratios (OR) and their 95% confidence intervals. Cases were born to mothers of a higher standard education, the OR for an increment of four schooling years being 1.48 (1.17-1.87) and had higher birth weight, the OR for an increment of 500g being 1.36 (1.04-1.77). Pet ownership and birth after a pregnancy with anaemia were associated with increased risk, the ORs being 2.18 (1.14-4.16) and 2.60 (1.39-4.86) respectively. From the frequency analyses, indicative inverse associations were found with birth order, household crowding and previous hospitalization with allergic diseases, whereas indicative positive associations were found with diabetes mellitus during pregnancy and with neonatal jaundice. Substantial or significant elevations were not found with respect to maternal smoking and coffee drinking during pregnancy, diagnostic radiography and ultrasonographic examinations or blood transfusions. A significant inverse association with maternal consumption of alcohol could be due to multiple comparisons, but a detrimental effect can probably be excluded. A non-significant positive association with total shots of viral vaccinations and a weak non-significant inverse association with breast feeding were also found. We interpret the findings of this study as being compatible with acute childhood leukaemia being linked with delayed development of herd immunity to fairly common infectious agents, in conjunction with accelerated perinatal and early post-natal growth. PMID:9365177

  17. The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias

    Directory of Open Access Journals (Sweden)

    Maher Eamonn R

    2009-07-01

    Full Text Available Abstract Background The Ras-assocation family (RASSF of tumour suppressor genes (TSGs contains 10 members that encode proteins containing Ras-assocation (RA domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1–10 in a series of childhood acute lymphocytic leukaemias (ALL and normal blood and bone marrow samples. Results COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51 B-ALL and 41% (12/29 T-ALL, whilst RASSF10 was methylated in 16% (8/51 B-ALL and 88% (23/26 T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC. Conclusion This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.

  18. Childhood leukaemia and non-Hodgkin's lymphoma near large rural construction sites, with a comparison with Sellafield nuclear site

    International Nuclear Information System (INIS)

    The objective was to determine whether population mixing produced by large, non-nuclear construction projects in rural areas is associated with an increase in childhood leukaemia and non-Hodgkin's lymphoma. A study was undertaken of the incidence of leukaemia and non-Hodgkin's lymphoma among children living near large construction projects in Britain since 1945, situated more than 20 km from a population centre, involving a workforce of more than 1000, and built over three or more calendar years. A 37% excess of leukaemia and non-Hodgkin's lymphoma at 0-14 years of age was recorded during construction and the following calendar year. The excesses were greater at times when construction workers and operating staff overlapped (72%), particularly in areas of relatively high social class. For several sites the excesses were similar to or greater than that near the nuclear site of Sellafield (67%), which is distinctive in its large workforce with many construction workers. Seascale, near Sellafield, with a ninefold increase had an unusually high proportion of residents in social class I. The findings support the infection hypothesis and reinforce the view that the excess of childhood leukaemia and non-Hodgkin's lymphoma near Sellafield has a similar explanation. (author)

  19. Spatial Patterns of Tungsten and Cobalt on Leaf Surfaces of Trees in Fallon, Nevada

    Science.gov (United States)

    Sheppard, P. R.; Hallman, C. L.; Ridenour, G.; Witten, M. L.

    2008-12-01

    Spatial patterns of airborne tungsten and cobalt are described from leaf surface chemistry of trees in Fallon, Nevada, where a cluster of childhood leukemia has been ongoing since 1997. In earlier research, airborne tungsten and cobalt have been shown to be elevated in total suspended particulates, surface dust, and lichens of Fallon. To update spatial patterns of airborne tungsten and cobalt in Fallon, leaves were collected in October 2007 from trees growing throughout Fallon. Collected leaves were measured for metals accumulated onto their surfaces. On Fallon leaf surfaces, tungsten and cobalt show maxima of 17 ppm and 6 ppm, respectively, near the center of town, north of Highway 50 and west of Highway 95. Background levels of tungsten and cobalt on leaves are ~0.50 ppm for both metals. These two peaks overlap spatially, and given the dense and widespread pattern of collection, the source area of these two airborne metals can be pinpointed to the vicinity of a hard-metal industry located north of Highway 50 and west of Highway 95. As an update of environmental research in Fallon, this leaf surface chemistry study adds to years of studies showing elevated airborne tungsten and cobalt in Fallon. Given the cluster of childhood leukemia in Fallon, it stands to reason that additional biomedical research is in order to test directly the leukogenicity of combined airborne tungsten and cobalt particulates.

  20. DNA incorporation of 6-thioguanine nucleotides during maintenance therapy of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma

    OpenAIRE

    Hedeland, Rikke L.; Hvidt, Kristian; Nersting, Jacob; Rosthøj, Susanne; Dalhoff, Kim; Lausen, Birgitte; Schmiegelow, Kjeld

    2009-01-01

    Abstract Purpose To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN), methylated metabolites (E-MeMP), Methotrexate polyglutamates (E-MTX), and to thiopurine methyltransferase activity (TPMT). ...

  1. Up-to-date monitoring of childhood cancer long-term survival in Europe: Leukaemias and lymphomas

    OpenAIRE

    Brenner, Hermann; Coebergh, Jan Willem; Parkin, D M; Izarzugaza, I.; Clavel, J; Arndt, Volker; Steliarova-foucher, E.

    2007-01-01

    textabstractBackground: In recent decades, following the introduction of effective chemotherapy, the prognosis of children with leukaemia and lymphoma has dramatically improved, but data reflecting further possible improvement achieved in the 1990s are scarce. Methods: Using the Automated Childhood Cancer Information (ACCIS) database, we carried out a period analysis of 10-year survival for the 1995-99 period. Analyses were carried out by diagnostic groups, age-group at diagnosis, sex and fou...

  2. Nuclear power plant and childhood leukaemia - Report by the pluralist working group

    International Nuclear Information System (INIS)

    nuclear power plant and the risk of leukaemia in children? There is no official answer to this question, barring that exposure to high doses or to high dose rates increases the risk. Many other genetic and environmental causes must also be taken into consideration, in order to prevent any misunderstanding. The molecular heterogeneity of leukaemia must also be taken into account when interpreting the data. Despite this complexity, the general public needs objective, comprehensible information. Scientists are under the obligation to meet the legitimate expectations of a society that is not only fully aware of its 'right to know', but is also eager for greater humanity and trust. For the reasons listed above, an independent, pluralist, technical working group composed of French and foreign experts with complementary skills and interests was created with the following mandate: - Issue an opinion on the available epidemiological knowledge of the effects of nuclear power plant (NPP), focusing in particular on the risk of childhood leukaemia; - Define the research needed to improve the existing data; - Help to deliver clear, transparent and regular information to the general public.; - Draw up guidelines for improving the existing knowledge on the link between childhood leukaemia and nuclear power plant (especially the impact of very low doses of ionising radiations). These guidelines will be made public. - Present the progress of this work to a national committee tasked with planning and monitoring the measures needed to improve the available knowledge of the effects of discharge from the nuclear industry on the health of people living nearby

  3. Birth characteristics and the risk of childhood leukaemias and lymphomas in New Zealand: a case-control study

    Directory of Open Access Journals (Sweden)

    Dockerty John D

    2006-09-01

    Full Text Available Abstract Background Some studies have found that lower parity and higher or lower social class (depending on the study are associated with increased risks of childhood acute lymphoblastic leukaemia (ALL. Such findings have led to suggestions that infection could play a role in the causation of this disease. An earlier New Zealand study found a protective effect of parental marriage on the risk of childhood ALL, and studies elsewhere have reported increased risks in relation to older parental ages. This study aimed to assess whether lower parity, lower social class, unmarried status and older parental ages increase the risk of childhood ALL (primarily. These variables were also assessed in relation to the risks of childhood acute non-lymphoblastic leukaemia, non-Hodgkin's lymphomas and Hodgkin's disease. Methods A case control study was conducted. The cases were 585 children diagnosed with leukaemias or lymphomas throughout New Zealand over a 12 year period. The 585 age and sex matched controls were selected at random from birth records. Birth records from cases (via cancer registration record linkage and from controls provided accurate data on maternal parity, social class derived from paternal occupation, maternal marital status, ages of both parents, and urban status based on the address on the birth certificate. Analysis was by conditional logistic regression. Results There were no statistically significant associations overall between childhood ALL and parity of the mother, social class, unmarried maternal status, increasing parental ages (continuous analysis, or urban status. We also found no statistically significant associations between the risks of childhood acute non-lymphoblastic leukaemia, non-Hodgkin lymphomas, or Hodgkin's disease and the variables studied. Conclusion This study showed no positive results though of reasonable size, and its record linkage design minimised bias. Descriptive studies (eg of time trends of ALL show that

  4. Childhood leukaemia and ordnance factories in west Cumbria during the Second World War.

    Science.gov (United States)

    Kinlen, L

    2006-07-01

    Much evidence has accumulated that childhood leukaemia (CL) is a rare response to a common, but unidentified, infection and in particular that situations involving the unusual mixing of urban and rural groups (approximating to, respectively, groups infected with, and susceptible to, the relevant microorganism) can produce localised epidemics with consequent increases of the infrequent leukaemic complication. During the Second World War, explosives production factories were built and operated at Drigg and Sellafield, and a shell filling factory at Bootle, in west Cumbria, England, requiring substantial numbers of construction workers to be brought into this remote and isolated area. Following the design of an earlier study of CL near large (post-war) rural construction sites, mortality from this disease was investigated with the help of the Office of National Statistics, in the area around these Cumbrian factories where local workers largely lived, during the construction period and with particular reference to the overlapping construction and operational phase when the mixing of local and migrant workers would have been greatest. An excess of leukaemia deaths at ages 1-14 was found during the construction period (observed 3; observed/expected (O/E) 2.2, 95% confidence interval (CI): 0.6, 6.0), which was more marked and statistically significant during the overlap with operations (O 3; O/E 4.5, 95% CI: 1.1, 12.2), especially at ages 1-4 (O 2; O/E 7.1, CI: 1.2, 23.6). A previous investigation did not detect this excess because it considered only a small part of west Cumbria that omitted the communities where most of the workforce lived, having incorrectly attributed the post-war expansion of the village of Seascale (situated between Drigg and Sellafield) to the wartime ordnance factories. The present findings are consistent with the results of the earlier study of rural construction projects and with the general evidence that marked rural-urban population mixing

  5. Risk factors of childhood leukaemia with a focus on environmental hazards; Leukaemien im Kindesalter und die Rolle von Umwelteinfluessen bei deren Entstehung

    Energy Technology Data Exchange (ETDEWEB)

    Schuez, J. [Inst. fuer Medizinische Biometrie, Epidemiologie und Informatik (IMBEI), Univ. Mainz, Mainz (Germany)

    2002-07-01

    Leukaemia is the most common malignancy in childhood. In Germany, there are annually about 620 new cases of childhood leukaemia among 13.2 million children. The causes of most leukaemias are still not known. Previous studies suggested a major role of environmental factors like low doses of ionizing radiation as well as electric and magnetic fields or pesticides. But recent studies contradict these assumptions. While weak associations between such factors and childhood leukaemia can not be ruled out, it can be estimated that they contribute at most to a minor fraction of leukaemias. Since leukaemia incidence is much higher in developed countries and since space-time clustering seems to be established for this disease, hypotheses involving a role of infectious agents have been put forward. Recent studies are suggestive that children with an appropriately modulated immune system have a lower risk of developing a leukaemia during childhood. As international collaborations emerge, it must be an aim that preventive actions are not only wishful thinking. (orig.) [German] Leukaemie ist die haeufigste Krebserkrankung im Kindesalter. In Deutschland erkranken von 13,2 Millionen Kindern unter 15 Jahren etwa 620 jaehrlich neu an Leukaemie. Die Ursachen von Leukaemien im Kindesalter sind auch heute noch weitgehend unklar. Umwelteinfluesse wie niedrige Dosen ionisierender Strahlung sowie nicht-ionisierende Strahlung oder Pestizide wurden lange verdaechtigt, einen Grossteil kindlicher Leukaemien zu verursachen. Inzwischen hat sich fuer die meisten Umweltfaktoren gezeigt, dass selbst wenn ein schwacher Zusammenhang mit dem Auftreten von Leukaemien im Kindesalter nicht ausgeschlossen werden kann, der Anteil dadurch verursachter Faelle doch eher gering ist. Die hoehere Inzidenz an Kinderleukaemie in den Industrielaendern sowie wiederholte Beobachtungen zeitlich begrenzter, regionaler Haeufungen an Leukaemieerkrankungen haben zu Hypothesen gefuehrt, die infektioesen Erregern eine

  6. Plasma high sensitivity troponin T levels in adult survivors of childhood leukaemias: determinants and associations with cardiac function.

    Directory of Open Access Journals (Sweden)

    Yiu-fai Cheung

    Full Text Available BACKGROUND: We sought to quantify plasma high sensitivity cardiac troponin (hs-cTnT levels, their determinants, and their associations with left ventricular (LV myocardial deformation in adult survivors of childhood acute leukaemias. METHODS AND RESULTS: One hundred adult survivors (57 males of childhood acute leukaemias, aged 24.1 ± 4.2 years, and 42 age-matched controls (26 males were studied. Plasma cTnT was determined using a highly sensitive assay. Genotyping of NAD(PH oxidase and multidrug resistance protein polymorphisms was performed. Left ventricular function was assessed by conventional, three-dimensional, and speckle tracking echocardiography. The medians (interquartile range of hs-cTnT in male and female survivors were 4.9 (4.2 to 7.2 ng/L and 1.0 (1.0 to 3.5 ng/L, respectively. Nineteen survivors (13 males, 6 females (19% had elevated hs-cTnT (>95(th centile of controls. Compared to those without elevated hs-TnT levels, these subjects had received larger cumulative anthracycline dose and were more likely to have leukaemic relapse, stem cell transplant, and cardiac irradiation. Their LV systolic and early diastolic myocardial velocities, isovolumic acceleration, and systolic longitudinal strain rate were significantly lower. Survivors having CT/TT at CYBA rs4673 had higher hs-cTnT levels than those with CC genotype. Functionally, increased hs-cTnT levels were associated with worse LV longitudinal systolic strain and systolic and diastolic strain rates. CONCLUSIONS: Increased hs-cTnT levels occur in a significant proportion of adult survivors of childhood acute leukaemias and are associated with larger cumulative anthracycline dose received, history of leukaemic relapse, stem cell transplant, and cardiac irradiation, genetic variants in free radical metabolism, and worse LV myocardial deformation.

  7. Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study.

    OpenAIRE

    Stiller, C A; Chessells, J M; Fitchett, M

    1994-01-01

    There is a well-known raised risk of leukaemia in children with neurofibromatosis type 1 (NF-1). We carried out the first detailed population-based study of leukaemia and non-Hodgkin lymphoma (NHL) associated with NF-1 in order to estimate the risk and elucidate the relationship between these conditions. Over the 17 year study period there were five cases of chronic myelomonocytic leukaemia (CMML) in patients with NF-1 (relative risk 221; 95% CI 71-514), 12 cases of acute lymphoblastic leukae...

  8. Temporal association between childhood leukaemia and population growth in Swiss municipalities.

    Science.gov (United States)

    Lupatsch, Judith E; Kreis, Christian; Zwahlen, Marcel; Niggli, Felix; Ammann, Roland A; Kuehni, Claudia E; Spycher, Ben D

    2016-08-01

    The population mixing hypothesis proposes that childhood leukaemia (CL) might be a rare complication of a yet unidentified subclinical infection. Large population influxes into previously isolated rural areas may foster localised epidemics of the postulated infection causing a subsequent increase of CL. While marked population growth after a period of stability was central to the formulation of the hypothesis and to the early studies on population mixing, there is a lack of objective criteria to define such growth patterns. We aimed to determine whether periods of marked population growth coincided with increases in the risk of CL in Swiss municipalities. We identified incident cases of CL aged 0-15 years for the period 1985-2010 from the Swiss Childhood Cancer Registry. Annual data on population counts in Swiss municipalities were obtained for 1980-2010. As exposures, we defined (1) cumulative population growth during a 5-year moving time window centred on each year (1985-2010) and (2) periods of 'take-off growth' identified by segmented linear regression. We compared CL incidence across exposure categories using Poisson regression and tested for effect modification by degree of urbanisation. Our study included 1500 incident cases and 2561 municipalities. The incident rate ratio (IRR) comparing the highest to the lowest quintile of 5-year population growth was 1.18 (95 % CI 0.96, 1.46) in all municipalities and 1.33 (95 % CI 0.93, 1.92) in rural municipalities (p value interaction 0.36). In municipalities with take-off growth, the IRR comparing the take-off period (>6 % annual population growth) with the initial period of low or negative growth (<2 %) was 2.07 (95 % CI 0.95, 4.51) overall and 2.99 (1.11, 8.05) in rural areas (p interaction 0.52). Our study provides further support for the population mixing hypothesis and underlines the need to distinguish take-off growth from other growth patterns in future research. PMID:27251152

  9. Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Schie, R.M. van; Bruggemann, R.J.M.; Hoogerbrugge, P.M.; Loo, D.M. te

    2011-01-01

    BACKGROUND: Vincristine is one of the cornerstones of the treatment of children with acute lymphoblastic leukaemia (ALL). Constipation, and peripheral and central neurotoxicities are the most common side effects. A comparative study exploring vincristine toxicity in individual patients receiving vin

  10. Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG)

    NARCIS (Netherlands)

    Groninger, E; Meeuwsen-de Boer, T; Koopmans, P; Uges, D; Sluiter, W; Veerman, A; Kamps, W

    2005-01-01

    The relationship between vincristine pharmacokinetics and its antileukaemic effect in children is unknown. Since vincristine plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL), it is worthwhile to explore if efficacy can be improved by individual dose adjustment. Ther

  11. Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG).

    NARCIS (Netherlands)

    Groninger, E.; Boer, T. de; Koopmans, P.P.; Uges, D.R.A.; Sluiter, W.J.; Veerman, A.; Kamps, W.; Graaf, S.S.N. de

    2005-01-01

    The relationship between vincristine pharmacokinetics and its antileukaemic effect in children is unknown. Since vincristine plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL), it is worthwhile to explore if efficacy can be improved by individual dose adjustment. Ther

  12. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia: biological background and prognostic impact. Results from the NOPHO ALL-92 and ALL-2000 studies

    DEFF Research Database (Denmark)

    Vaitkeviciene, G; Forestier, E; Hellebostad, M;

    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...

  13. Vincristine in childhood leukaemia : no pharmacokinetic rationale for dose reduction in adolescents

    NARCIS (Netherlands)

    Frost, BM; Lonnerholm, G; Koopmans, P; Abrahamsson, J; Behrendtz, M; Castor, A; Forestier, E; Uges, DRA

    2003-01-01

    Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on

  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. A comparison between the risks of childhood leukaemia from parental exposure to radiation in the Sellafield workforce and those displayed among the Japanese bomb survivors

    International Nuclear Information System (INIS)

    The cases of childhood leukaemia found near the Sellafield plant and those observed in the offspring of the Japanese bomb survivors are analysed using a relative risk model. The leukaemia relative risk coefficients for total paternal (whole-body) pre-conception exposure for the Sellafield children are found to be about 50 to 80 times higher than the (gonadal) coefficients applying to the offspring of the bomb survivors. This difference is statistically significant, and in particular the risk coefficients for the Sellafield cohort are significantly positive, unlike those for the Japanese. If the assumption is made that the excess relative risk estimated from the Sellafield data lasts for the whole of the life of the offspring, the apparent population leukaemia risk to the first-generation offspring (for an England and Wales population) would be between 4% Sv-1 and 5% Sv-1. (author)

  16. Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study

    Directory of Open Access Journals (Sweden)

    Skegg David CG

    2007-07-01

    Full Text Available Abstract Background An earlier case-control study from Western Australia reported a protective effect of maternal folic acid supplementation during pregnancy on the risk of childhood acute lymphoblastic leukaemia (ALL. The present study tested that association. Methods A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy. Results There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR 1.1, 95% confidence interval (CI 0.5–2.7. Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8–1.1. Conclusion Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.

  17. Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of iBFM-SG

    OpenAIRE

    Harrison, Christine J; Haas, Oskar A.; Harbott, W; Biondi, Andrea; Stanulla, Martin; Trka, Jan; Izraeli, Shai

    2010-01-01

    Abstract Treatment of childhood acute lymphoblastic leukaemia (ALL) has improved considerably in recent years. A contributing factor has been the improved stratification for treatment according to a number of factors including genetic determinants of outcome. Here we review the current diagnostic criteria of genetic abnormalities in precursor B-ALL (BCP-ALL), including the relevant technical approaches and the application of the most appropriate methods for the detection of each ab...

  18. After the chemotherapy: potential mechanisms for chemotherapy-induced delayed skeletal muscle dysfunction in survivors of acute lymphoblastic leukaemia in childhood

    OpenAIRE

    Celena eScheede-Bergdahl; R Thomas Jagoe

    2013-01-01

    There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukaemia (ALL), have increased rates of longterm skeletal muscle dysfunction. This places them at higher risk of physical restriction and functional impairment as well as potentially contributing to observed increases in cardiovascular disease and insulin resistance in later life. The mechanisms underlying these changes in skeletal muscle are unknown but chemotherapy drugs used in treatment for ALL are strong...

  19. Rural population mixing and childhood leukaemia: effects of the North Sea oil industry in Scotland, including the area near Dounreay nuclear site

    International Nuclear Information System (INIS)

    The objective of this study was to determine if any excess of childhood leukaemia and non-Hodgkin's lymphoma was associated with certain striking examples of population mixing in rural Scotland produced by the North Sea oil industry. Details were traced for over 30 000 workers (25 yrs old) involved in the construction of the large oil terminals in the Shetland and Orkney islands in northern Scotland or employed offshore. Home addresses of the 17160 Scottish residents were postcoded, integrated with census data, and then classified as urban or rural. Rural postcode sectors, ranked by proportion of oil workers, were grouped into three categories with similar numbers of children but contrasting densities of oil workers. The incidence of leukaemia and non-Hodgkin's lymphoma was examined in these rural (and also in urban) categories in the periods 1974-8, 1979-83 and 1984-8. A significant excess of leukaemia and non-Hodgkin's lymphoma was found in 1979-83 in the group of rural home areas with the largest proportion of oil workers, following closely on large increases in the workforce. The area near the Dounreay nuclear installation, where an excess of leukaemia is already well known, was within the rural high oil category. (Author)

  20. [Childhood leukaemia in a residential area with a high-voltage power line: approach according to the Dutch Community Health Services' guideline 'Cancer Clusters'].

    Science.gov (United States)

    Hegger, Carola; Reedijk, Ardine M J

    2013-01-01

    The new Dutch Community Health Services' (GGD) guideline titled 'Cancer Clusters' describes a phased plan for investigating reported cancer clusters. In each phase, attention is paid to both health and environmental issues and their possible links to one another. Throughout the entire cluster investigation, good risk communication is essential. In accordance with the new guideline, the Rotterdam-Rijnmond Public Health Services investigated the incidence of childhood leukaemia in a residential area as well as the data available on the high-voltage power line located there. More children in this residential area had been diagnosed with leukaemia than expected. However, the children had not been subjected to prolonged exposure to strong magnetic fields emitted from the high-voltage power line. With this type of cluster investigation, it is not possible to establish a causal relationship between childhood leukaemia and high-voltage power lines. However, the research did provide stakeholders insight into the health-and-environment situation and thereby, the opportunity to assess the situation appropriately and to act accordingly, if desired.

  1. Quantification of TEL-AML1 transcript for minimal residual disease assessment in childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Drunat, S; Olivi, M; Brunie, G; Grandchamp, B; Vilmer, E; Bièche, I; Cavé, H

    2001-08-01

    Strategies currently used for residual disease detection in acute lymphoblastic leukaemia (ALL) rely on polymerase chain reaction (PCR) detection of immunoglobulin and T-cell receptor rearrangements. The TEL-AML1 fusion transcript, which is associated with t(12;21) (p13;q22), is found in 25% of childhood B-cell precursor ALL, and represents an interesting alternative target. We compared two methods for quantitating TEL-AML1 fusion transcripts: competitive PCR and real-time PCR. These techniques showed similar sensitivity (5 x 10(-5)) and reproducibility. Giving highly correlated results, both techniques can be conveniently used for TEL-AML1 transcript quantification. The constancy of TEL-AML1 expression was evaluated by measuring TEL-AML1 transcripts at different steps of the cell cycle, and in 21 cases of ALL at diagnosis. No major variation in TEL-AML1 expression was observed during the cell cycle or in 20/21 of the ALL patients. Residual disease was then determined after completion of induction therapy in 20 patients with a TEL-AML1-positive ALL. Seven patients out of 20 (35%) were still positive, including two patients with high level of residual blasts (close to or beyond 10(-2)). When comparison was possible, results obtained using TEL-AML1 quantification were in accordance with those obtained using T-cell receptor rearrangements analysis.

  2. Distance to high-voltage power lines and risk of childhood leukaemia

    DEFF Research Database (Denmark)

    Pedersen, Camilla; Bräuner, Elvira; Rod, Naja Hulvej;

    2014-01-01

    significant interaction between distance to nearest power line and domestic radon regarding risk of childhood leukemia (p = 0.01) when using the median radon level as cut-off point but not when using the 75th percentile (p = 0.90). We found no evidence of an interaction between distance to nearest power line...

  3. Neurotoxicity during induction treatment of childhood acute lymphoblastic leukaemia: Two case reports

    Directory of Open Access Journals (Sweden)

    Kostić Gordana

    2009-01-01

    Full Text Available Introduction. During chemotherapy of acute lymphoblastic leukaemia (ALL, children sometimes exhibit neurological disturbances. Chemiotherapeutic regimens include methotrexate, administered either intravenously or via intrathecal route. Although multiple drugs are used in addition to methotrexate, the acute neurotoxicity reported in patients is usually attributed to methotrexate. The acute neurotoxicity usually results in stroke-like symptoms such as aphasia, weakness, sensory deficits, ataxia and seizures. Outline of Cases. From 2002 until January 2008, 32 children with ALL were diagnosed and treated at the Children's Hospital in Niš. The patients' age ranged from 1.5 to 16 years. They were treated in accordance with the protocol ALL IC-BFM 2002 (ALL Intercontinental Berlin Frankfurt M'nster 2002. Two of the patients (6.25% exhibited neurotoxicity. After the occurrence of neurological symptoms, the patients were ophthalmologically and neurologically examined. In addition, the magnetic resonance (MR imaging, computerized tomography and electroencephalography were applied. The paper presents two patients, aged 9 and 15 years respectively, who exhibited acute neurotoxicity - methotrexate encephalopathy during ALL treatment. Both patients had tonic-clonic seizures and neurological symptoms in the course of the induction therapy. Neurotoxicity occurred 7 days after the third, and 3 days after the fourth intrathecal methotrexate therapy. MR images confirmed multi-focal morphological changes of brain density in one of the patients, while the other patient had normal CT reading. Even though the development significantly differed, the changes were reversible in both patients. Conclusion. The neurotoxicity in patients with ALL can be combined with significant structural changes of the brain, but also morphological changes can be absent. Several questions concerning aetiology and treatment of neurological events are raised.

  4. Multi-model inference of adult and childhood leukaemia excess relative risks based on the Japanese A-bomb survivors mortality data (1950-2000).

    Science.gov (United States)

    Walsh, Linda; Kaiser, Jan Christian

    2011-03-01

    Some relatively new issues that augment the usual practice of ignoring model uncertainty, when making inference about parameters of a specific model, are brought to the attention of the radiation protection community here. Nine recently published leukaemia risk models, developed with the Japanese A-bomb epidemiological mortality data, have been included in a model-averaging procedure so that the main conclusions do not depend on just one type of model or statistical test. The models have been centred here at various adult and young ages at exposure, for some short times since exposure, in order to obtain specially computed childhood Excess Relative Risks (ERR) with uncertainties that account for correlations in the fitted parameters associated with the ERR dose-response. The model-averaged ERR at 1 Sv was not found to be statistically significant for attained ages of 7 and 12 years but was statistically significant for attained ages of 17, 22 and 55 years. Consequently, such risks when applied to other situations, such as children in the vicinity of nuclear installations or in estimates of the proportion of childhood leukaemia incidence attributable to background radiation (i.e. low doses for young ages and short times since exposure), are only of very limited value, with uncertainty ranges that include zero risk. For example, assuming a total radiation dose to a 5-year-old child of 10 mSv and applying the model-averaged risk at 10 mSv for a 7-year-old exposed at 2 years of age would result in an ERR=0.33, 95% CI: -0.51 to 1.22. One model (United Nations scientific committee on the effects of atomic radiation report. Volume 1. Annex A: epidemiological studies of radiation and cancer, United Nations, New York, 2006) weighted model-averaged risks of leukaemia most strongly by half of the total unity weighting and is recommended for application in future leukaemia risk assessments that continue to ignore model uncertainty. However, on the basis of the analysis

  5. After the chemotherapy: potential mechanisms for chemotherapy-induced delayed skeletal muscle dysfunction in survivors of acute lymphoblastic leukaemia in childhood

    Directory of Open Access Journals (Sweden)

    Celena eScheede-Bergdahl

    2013-04-01

    Full Text Available There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukaemia (ALL, have increased rates of longterm skeletal muscle dysfunction. This places them at higher risk of physical restriction and functional impairment as well as potentially contributing to observed increases in cardiovascular disease and insulin resistance in later life. The mechanisms underlying these changes in skeletal muscle are unknown but chemotherapy drugs used in treatment for ALL are strongly implicated. Normal skeletal muscle growth, development and function are dependent on correctly functioning muscle satellite cells, muscle motor neurons and muscle mitochondria. Each of these key components is potentially susceptible to damage by chemotherapy in childhood, particularly prolonged courses including repeated administration of combination chemotherapy. If this chemotherapy-induced damage is not fully reversible, impairment of satellite cells, muscle motor innervation and mitochondria could, either singly or together, lead to the emergence of delayed or persistent skeletal muscle dysfunction many years later. The known effects of individual drugs used in the treatment of ALL are outlined and the need for specific targeted studies to investigate the mechanisms underlying persistent muscle dysfunction in survivors of childhood cancers is highlighted.

  6. Development of remedial process options: Phase II, Feasibility study: Installation Restoration Program, Naval Air Station Fallon, Fallon, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Cronk, T.A.; Smuin, D.R. (Oak Ridge National Lab., TN (United States)); Schlosser, R.M. (Oak Ridge Associated Universities, Inc., TN (United States))

    1991-11-01

    This technical memorandum develops process options which are appropriate for environmental restoration activities at Naval Air Station Fallon (NAS Fallon), Nevada. Introduction of contaminants to the environment has resulted from deliberate disposal activities (both through dumping and landfilling) and accidental spills and leaks associated with normal activities at NAS Fallon over its lifetime of operation. Environmental sampling results indicate that the vast majority of contaminants of concern are petroleum hydrocarbon related. These contaminants include JP-4, JP-5, leaded and unleaded gasoline, waste oils and lubricants, hydraulic fluids, and numerous solvents and cleaners. The principal exposure pathways of concern associated with NAS Fallon contaminants appear to be the surface flows and shallow drainage systems to which the base contributes. Available data indicate NAS Fallon IR Program sites are not contributing excessive contamination to surface flows emanating from the base. Contaminants appear to be contained in a relatively immobile state in the shallow subsurface with little or no contaminant migration off site.

  7. Outcome after cessation of therapy in childhood acute lymphoblastic leukaemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP).

    Science.gov (United States)

    Jankovic, M; Fraschini, D; Amici, A; Aricò, M; Arrighini, A; Basso, G; Colella, R; DiTullio, M T; Haupt, R; Macchia, P

    1993-01-01

    A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P 20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

  8. Treatment on leukaemia in children

    Energy Technology Data Exchange (ETDEWEB)

    McCann, S.R. (St. James' s Hospital, Dublin (Ireland))

    1984-06-01

    Since the late 1960s it has become clear that significant numbers of children may achieve long term remissions from acute leukaemia and that substantial numbers are probably cured of their disease. Results in most European countries and North America have failed to demonstrate any improvement on the early ''success'' rates and more than 50% of children will still ultimately die from their diseases. This review will attempt to outline the results of current approaches and treatment, to highlight prognostic factors and to examine the role of bone marrow transplantation in a onetime invariably fatal disease. For the purpose of this review, acute lymphoblastic leukaemia (ALL) only, will be dealt with in detail, as this accounts for 85% of cases of childhood acute leukaemia. 27 refs.

  9. Slower early response to treatment and distinct expression profile of childhood high hyperdiploid acute lymphoblastic leukaemia with DNA index < 1.16.

    Science.gov (United States)

    Zaliova, Marketa; Hovorkova, Lenka; Vaskova, Martina; Hrusak, Ondrej; Stary, Jan; Zuna, Jan

    2016-09-01

    Acute lymphoblastic leukaemias (ALL) with 51-67 chromosomes are defined as high hyperdiploid (HHD) and are generally associated with good prognosis. However, several studies show heterogeneity in HHD ALL and suggest that the favourable prognosis is associated rather with higher ploidy defined by DNA index (DNAi) ≥ 1.16 or with a presence of specific single or combined trisomies. HHD ALL with DNAi < 1.16 are only rarely studied separately. Using single nucleotide polymorphism array, we analysed 89 childhood HHD ALL patients divided into groups with lower (<1.16; n = 34) and higher (≥1.16; n = 55) DNAi. We assessed treatment response, presence of secondary aberrations, mutations in RAS pathway genes and CREBBP and also gene expression profile (GEP) to reveal differences between the two subgroups. Cases with 51-54 chromosomes had DNAi 1.1-1.16 and cases with 55-67 chromosomes had DNAi ≥ 1.16. The groups with lower and higher DNAi had distinct response to early treatment and distinct GEP. The better response of the group with higher DNAi was associated with specific trisomies (trisomy of chromosome 10 or combined with trisomies 4 and/or 17). Our results suggest that cytogenetically defined HHD ALL can in fact be divided into two biologically distinguishable subgroups and that DNAi 1.16 is a relevant value to separate between the two. © 2016 Wiley Periodicals, Inc. PMID:27163296

  10. The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI

    Directory of Open Access Journals (Sweden)

    Vargha-Khadem Faraneh

    2011-10-01

    Full Text Available Abstract Background The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS directed therapies in childhood acute lymphoblastic leukaemia (ALL. To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1 all patients (n = 555 versus related controls (n = 311, (2 low-risk children (presenting white cell count (WCC 9/l randomised to intrathecal methotrexate (n = 197 versus intrathecal and high-dose intravenous methotrexate (HDM (n = 202, and (3 high-risk children (WCC ≥ 50 × 109/l, age ≥ 2 years randomised to HDM (n = 79 versus cranial irradiation (n = 77. Results There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P Conclusion Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes. Trial registration ISRCTN: ISRCTN16757172

  11. Leukaemia incidence and survival in children and adolescents in Europe during 1978-1997. Report from the Automated Childhood Cancer Information System project

    NARCIS (Netherlands)

    Coebergh, J. W. W.; Reedijk, A. M. J.; de Vries, E.; Martos, C.; Jakab, Z.; Steliarova-Foucher, E.; Kamps, W. A.

    2006-01-01

    Leukaemias constitute approximately one-third of cancers in children (age 0-14 years) and 10% in adolescents (age 15-19 years). Geographical patterns (1988-1997) and time trends (1978-1997) of incidence and survival from leukaemias in children (n = 29,239) and adolescents (n = 1929) were derived fro

  12. The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia: an open-label study

    Directory of Open Access Journals (Sweden)

    van Coeverden Silvia CCM

    2008-06-01

    Full Text Available Abstract Background To reduce the risk of brain damage children with acute lymphoblastic leukaemia (ALL are nowadays mainly treated with intrathecal chemotherapy (ITC instead of central nervous system (CNS radiation therapy (CRT to prevent CNS relapse. However, chemotherapy may also lead to cognitive deficits. As growth hormone deficiency (GHD or impaired growth hormone secretion are frequently found in ALL patients treated with cranial radiation therapy and/or chemotherapy, we hypothesized that GH therapy may reduce cognitive deficits in these patients. Methods Twenty young adult survivors of childhood ALL with reduced bone mineral density ( IQ and neuropsychological performance were assessed at pre-treatment (T1 and after one (T2 and two (T3 years. ANOVA was performed with assessment at T1, T2 and T3 as repeated measurements factor. Relations between test score changes and changes of IGF-I levels were determined by calculating the Pearson correlation coefficient. Results Scores on the cognitive tests were in the normal range. Verbal short- and long-term memory performance decreased between T1 and T2, and increased between T2 and T3. Performance at T3 was not significantly different from that at T1. Performance for sustained attention improved from T1 to T2 and from T1 to T3. Visual-spatial memory was improved after one year of GH treatment. A significant positive correlation was found for Δ IGF-I (T2-T1 with difference scores of visual-spatial memory (T2-T1 and T3-T1, indicating that IGF-I increase after one year of GH treatment is associated with increase in cognitive-perceptual performance at month 12 and 24. Conclusion Since the level of intellectual functioning of our patient cohort was in the normal range the present finding that GH treatment has negative effects on verbal memory and positive on attention and visual-spatial memory warrants similar studies in other groups of ALL survivors. Also, a lower dose of GH should be determined

  13. Adjuvant low dose radiation in childhood T cell leukaemia/lymphoma (report from the United Kingdom Childrens' Cancer Study Group--UKCCSG).

    OpenAIRE

    Mott, M G; Chessells, J M; Willoughby, M L; Mann, J R; Morris-Jones, P H; Malpas, J S; Palmer, M K

    1984-01-01

    From November 1977 to July 1983, 82 children with T leukaemia/lymphoma entered a randomised trial of combination chemotherapy and radiotherapy. Twenty-five were designated T lymphoma and 57 T leukaemia, 28 having greater than 100 x 10(9)1(-1) blasts in peripheral blood at diagnosis. Twenty-seven patients with mediastinal primaries who were treated on the companion non-Hodgkin lymphoma (NHL) trial were comparable in all respects to the T lymphoma patients and the results of treatment were ther...

  14. Nuclear power and leukaemia

    International Nuclear Information System (INIS)

    This booklet describes the nature of leukaemia, disease incidence in the UK and the possible causes. Epidemiological studies observing rates of leukaemia near nuclear power stations in the UK and other parts of the world are discussed. Possible causes of leukaemia excesses near nuclear establishments include radioactive discharges into the environment, paternal radiation exposure and viral causes. (UK)

  15. In vitro drug resistance and prognostic impact of p16(INK4A)/p15(INK4B) deletions in childhood T-cell acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Ramakers-van Woerden, NL; Pieters, R; Slater, RM; Loonen, A.H.; Beverloo, HB; van Drunen, E; Heyman, M; Moreno, TC; Rots, MG; van Wering, ER; Kamps, WA; Janka-Schaub, GE; Veerman, AJP

    2001-01-01

    p16 gene deletions are present in about 70% of primary paediatric T-cell acute lymphoblastic leukaemia (T-ALL) and 20% of common/precursor B-cell ALL cases. It is not clear what the impact of the frequent p16 deletions is within the subgroup of T-lineage ALL. We studied the relationship between p16/

  16. Leukaemia and lymphoma near the Sellafield reprocessing plant

    International Nuclear Information System (INIS)

    Studies have shown an excess of childhood leukaemia near nuclear establishments but have been unable to establish whether known causes or factors associated with the nuclear plants themselves are responsible for the observed excess. Such an association has, however, been discovered in a study where the recorded external dose of whole-body ionizing radiation to fathers working at Sellafield is associated with the development of leukaemia among their children. A circle, centered on the Sellafield nuclear plant, of radius 5 kilometers contained a cluster of 5 cases of leukaemia and 3 cases of non-Hodgkin's lymphoma in children. All the leukaemias and 2 of the 3 lymphomas occurred in children born to parents living in Seascale, a village some 3 kilometers from the nuclear plant. Taking the national incidence of childhood leukaemia, less than one case of leukaemia would be expected in Seascale. The finding that 'exposure of fathers to ionising radiation before conception is related to the development of leukaemia in their offspring' is the first such finding with human data

  17. Acute lymphocytic leukaemia in children in the Netherlands

    International Nuclear Information System (INIS)

    Some features, present at diagnosis in children with acute lymphocytic leukaemia, investigated during the period 1973-1975, and the results of treatment according to protocol AL II of the Dutch Childhood Leukaemia Study Group (SNWLK), are described. This report concerns the results of induction treatment, elective treatment of the central nervous system, and also of the prospective comparative study on the influence of the addition of cyclophosphamide to maintenance treatment with 6-mercaptopurine and methotrextate. In the context of the investigation of long-term side effects of disease and treatment, the immunocompetence of children with acute lymphocytic leukaemia in continuous remission after cessation of therapy was studied. (Auth.)

  18. Antibiotic use from conception to diagnosis of child leukaemia as compared to the background population

    DEFF Research Database (Denmark)

    Gradel, Kim Oren; Kaerlev, Linda

    2015-01-01

    BACKGROUND: The role of infection in the aetiology of childhood leukaemia is unknown. We used prescriptions of antibiotics from Danish pharmacies as a proxy measure for the occurrence of infections. PROCEDURE: We investigated the association between exposure to antibiotics, from conception to...... leukaemia diagnosis, and the risk of leukaemia. Incident cases of leukaemia among children in Denmark, 1995-2008, with mothers having their earliest conception date in 1995, were individually matched to population controls by age, sex and municipality. Conditional logistic regression analyses assessed...... antibiotic redemptions in different time periods from conception up to 6 months before the diagnoses of all leukaemia types, acute lymphoblastic leukaemia [ALL] and ALL in 2- to 5-year-old children, adjusting for several potential confounders. RESULTS: A total of 120/360 (33.3%) leukaemia mothers and 1...

  19. Cytochemical studies in leukaemias

    Directory of Open Access Journals (Sweden)

    Batra Neelam

    1978-01-01

    Full Text Available One hundred cases of acute leukaemia were studied, by Romanowsky stains and by cytochemical stains such as Sudan Black B, Periodic Acid Schiff, Alkaline phosphatase and Peroxidase stains. Cases difficult to diagnose by Romanowsky stained smears were easily classified by these supplementary stains. Their importance as supplements to the routine Romanowsky staining in the diagnosis of leukaemia is emphasized and the division of acute lymphoblastic leukaemia based on these patterns is suggested.

  20. Case-control study of leukaemia among young people near La Hague nuclear reprocessing plant: the environmental hypothesis revisted

    International Nuclear Information System (INIS)

    The objective is to investigate the association between childhood leukaemia and established risk factors or other factors related to La Hague nuclear waste reprocessing plant. There is some convincing evidence in childhood leukaemia of a causal role for environmental radiation exposure from recreational activities on beaches. New methods for identifying the environmental pathways, focusing on marine ecosystems, are warranted. (author)

  1. Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Henriksen, Louise T; Nersting, Jacob; Raja, Raheel A;

    2014-01-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The...

  2. Interphase fluorescent in situ hybridization deletion analysis of the 9p21 region and prognosis in childhood acute lymphoblastic leukaemia (ALL)

    DEFF Research Database (Denmark)

    Kuchinskaya, Ekaterina; Heyman, Mats; Nordgren, Ann;

    2011-01-01

    Interphase fluorescent in situ hybridization (FISH) was applied on diagnostic BM smears from 519 children with acute lymphoblastic leukaemia (ALL) in order to establish the frequency and prognostic importance of 9p21 deletion in children enrolled in the Nordic Society of Paediatric Haematology and...... Oncology (NOPHO) - 2000 treatment protocol. Among the patients, 452 were diagnosed with B-cell precursor (BCP)-ALL and 66 with T-ALL. A higher incidence of 9p21 deletions was found in T-ALL (38%) compared to BCP-ALL (15·7%). Homozygous deletions were found in 19·7% of T-ALL and 4·0% of BCP-ALL; hemizygous...

  3. Outcome of ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol: frequent late relapses but good overall survival

    DEFF Research Database (Denmark)

    Forestier, E.; Heyman, M.; Andersen, Mette Klarskov;

    2008-01-01

    The prognostic impact of t(12;21)(p13;q22) [ETV6/RUNX1 fusion] in paediatric acute lymphoblastic leukaemia (ALL) has been extensively debated, particularly with regard to the frequency of late relapses and appropriate treatment regimens. We have retrospectively collected 679 ALLs with known ETV6....../RUNX1 status, as ascertained by fluorescence in situ hybridization or reverse-transcription polymerase chain reaction, treated according to the Nordic Society of Paediatric Haematology and Oncology -ALL-1992 protocol. The assigned risk groups/treatment modalities for the 171 (25%) patients with t(12...... almost 50% of all relapses occurring > or = 5 years after diagnosis. Of all relapses after 6 years, 80% occurred in the t(12;21)-positive group. The overall survival was 94% at 5 years and 88% at 10 years; thus, the treatment of patients in second or later remission is usually successful. As yet, there...

  4. Leukaemia in East Suffolk

    International Nuclear Information System (INIS)

    An investigation was conducted by the East Suffolk Health Authority to determine whether there were any geographical variations in the incidence of leukaemia over the last fifteen years in East Suffolk suggesting an environmental hazard, e.g. Sizewell Power Station. No areas were found to have a statistically significant increased incidence of leukaemia cases although there did appear to be a cluster of cases in the Leiston area. (U.K.)

  5. Leukaemia and non-Hodgkin's lymphoma in young persons resident in small areas of West Cumbria in relation to paternal preconceptional irradiation.

    OpenAIRE

    Wakeford, R.; Parker, L.

    1996-01-01

    The results of a previous study suggested that an association between childhood leukaemia and the radiation dose received occupationally by a father before the conception of his child might provide the explanation for the marked excess of childhood leukaemia and non-Hodgkin's lymphoma in the village of Seascale, West Cumbria. The present study identifies other small areas (electoral wards) in West Cumbria where excess cases of leukaemia and non-Hodgkin's lymphoma in young people have occurred...

  6. Regenerating normal B-cell precursors during and after treatment of acute lymphoblastic leukaemia : implications for monitoring of minimal residual disease

    NARCIS (Netherlands)

    van Wering, ER; Van der Linden-Schrever, BEM; Szczepanski, T; Willemse, MJ; Baars, EA; Van Wijngaarde-Schmitz, HM; Kamps, WA; Van Dongen, JJM

    2000-01-01

    We studied 57 childhood acute lymphoblastic leukaemia (ALL) patients who remained in continuous complete remission after treatment according to the Dutch Childhood Leukaemia Study Group ALL-8 protocols. The patients were monitored at 18 time points during and after treatment [640 bone marrow (BM) an

  7. Distance to high-voltage power lines and risk of childhood leukaemia – an analysis of confounding by and interaction with other potential risk factors

    DEFF Research Database (Denmark)

    Pedersen, Camilla; Bräuner, Elvira V.; Rod, Naja H.;

    2014-01-01

    We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters...... the association between distance to nearest power line and childhood leukemia. We included 1024 cases aged .... We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door) were estimated using validated models. We found a statistically...

  8. Outcome of central nervous system relapses in childhood acute lymphoblastic leukaemia--prospective open cohort analyses of the ALLR3 trial.

    Directory of Open Access Journals (Sweden)

    Ashish Narayan Masurekar

    Full Text Available The outcomes of Central Nervous System (CNS relapses in children with acute lymphoblastic leukaemia (ALL treated in the ALL R3 trial, between January 2003 and March 2011 were analysed. Patients were risk stratified, to receive a matched donor allogeneic transplant or fractionated cranial irradiation with continued treatment for two years. A randomisation of Idarubicin with Mitoxantrone closed in December 2007 in favour of Mitoxantrone. The estimated 3-year progression free survival for combined and isolated CNS disease were 40.6% (25·1, 55·6 and 38.0% (26.2, 49.7 respectively. Univariate analysis showed a significantly better survival for age <10 years, progenitor-B cell disease, good-risk cytogenetics and those receiving Mitoxantrone. Adjusting for these variables (age, time to relapse, cytogenetics, treatment drug and gender a multivariate analysis, showed a poorer outcome for those with combined CNS relapse (HR 2·64, 95% CI 1·32, 5·31, p = 0·006 for OS. ALL R3 showed an improvement in outcome for CNS relapses treated with Mitoxantrone compared to Idarubicin; a potential benefit for matched donor transplant for those with very early and early isolated-CNS relapses.Controlled-Trials.com ISRCTN45724312.

  9. 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

  10. Stillwater Wildlife Management Area, Anaho Island National Wildlife Refuge and Fallon National Wildlife Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Fallon, Stillwater and Anaho Island National Wildlife Refuges are located in northwest Nevada and are administered by the refuge administrative office in...

  11. Leukaemia near british nuclear installations. Leucemies autour des installations nucleaires anglaises

    Energy Technology Data Exchange (ETDEWEB)

    Hubert, D. (Electricite de France (EDF), 75 - Paris (FR))

    1991-01-01

    An excess of childhood leukaemia has been seen near some British nuclear installations, especially near the Sellafield reprocessing plant. The same result was found in a more general study including a large number of nuclear sites. Similar studies made in USA, Canada and France have been negative. Moreover, epidemiological studies made in England have discovered other childhood leukaemia clusters in areas far from nuclear facilities, and especially near potential sites of nuclear installations. Several explanations are suggested but no definite conclusion is yet possible. Doses from radioactive releases seem to be too low to account for the additional deaths from leukaemia by environmental contamination. A virus activation, which might be associated with population influx into rural isolated areas, has been considered. The hypothesis of genetic mutation induced by ionising radiation in the fathers of children with leukaemia has been made because a higher risk of leukaemia was observed for children of fathers employed at Sellafield. No firm conclusion is possible considering the small number of observed cases and the lack of excess leukaemias in the offspring of Hiroshima and Nagasaki survivors. The possibility of internal contamination, chemicals or even radon is discussed as other causes. Studies in progress might allow to find an answer to the problem of leukaemia in the vicinity of British nuclear installations.

  12. Dicentric chromosome in the bone marrow of a child with megakaryoblastic leukaemia and Down's syndrome.

    OpenAIRE

    Wilkie, A O; Kitchen, C.; Oakhill, A; Howell, R T; Berry, P J

    1988-01-01

    A two year old girl with Down's syndrome (constitutional karyotype: 47 + 21), presenting with pancytopenia, developed acute megakaryoblastic leukaemia (AMKL). Her bone marrow contained an abnormal clone with a novel dicentric chromosome derived from chromosomes 5 and 7 (karyotype 46, XX, -5, -7, +dic (5;7) (p 13; p 11.2), +21. This case provides further evidence for a connection between chromosome 21 and this unusual form of childhood leukaemia, and raises questions about the loss of short ar...

  13. Treating childhood acute lymphoblastic leukaemia (ALL): summary of ten years' experience in Italy. ALL Steering Committee of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

    Science.gov (United States)

    Paolucci, G; Masera, G; Vecchi, V; Marsoni, S; Pession, A; Zurlo, M G

    1989-01-01

    Between 1976 and 1986, 2,093 children with ALL were enrolled in three consecutive generations of trials conducted by the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP). A 50% event-free survival at 5 years was achieved overall in this population, approximately accounting for more than 50% of the entire childhood ALL population in Italy. Participation in the group protocols increased from the original seven founding centers to the current 37 institutions. Results in the standard population (non-T immunophenotype, non-FAB L3, and less than 50,000 white blood cells (WBC/ml) were considerably better with more recent, more aggressive protocols. The two major results in this population (N = 540) were a relatively low incidence (8% at 5 years) of central nervous system (CNS) relapse in the "good"-risk population (less than 10,000 WBC, ages 3-6 years, and FAB L1), without the use of cranial irradiation, and a projected 4-year disease-free interval for bone-marrow relapse of 80% in the "average"-risk group, where a three-drug reinduction program was adopted after consolidation. Overall, the event-free survival of the most recent generation (protocol 82, median follow-up time of 38 months) is 66% at 4 years (95% confidence limits [CL] 61-71). Based on these 10 years of experience, the general strategy of the group for the 90s is outlined and discussed.

  14. Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission. Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

    Science.gov (United States)

    Uderzo, C; Valsecchi, M G; Balduzzi, A; Dini, G; Miniero, R; Locatelli, F; Rondelli, R; Pession, A; Arcese, W; Bacigalupo, A; Polchi, P; Andolina, M; Messina, C; Conter, V; Aricó, M; Galimberti, S; Masera, G

    1997-02-01

    We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study. All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation (n = 25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59-3.24), 0.69 (CI 0.27-1.77) and 0.35 (CI 0.06-1.91), with an overall non-significant difference between the two groups (P = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR). The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.

  15. Chilblain-like leukaemia cutis.

    Science.gov (United States)

    Tran, Chi; McEwen, Gary; Fraga, Garth Robert

    2016-01-01

    Chilblain, also known as pernio, is an abnormal inflammatory response to cold, moist environmental conditions. Persistent or atypical lesions should prompt investigation to exclude underlying systemic illness. We describe a case of acute myeloid leukaemia that presented with chilblain-like leukaemia cutis. PMID:27095810

  16. The chronic leukaemias

    Directory of Open Access Journals (Sweden)

    Peter Jacobs

    1989-09-01

    Full Text Available The slow progression of both chronic granulocytic and lymphocytic leukaemia, when compared to their acute counterparts, has been used as an argument to support less aggressive therapy or even, in some instances, a watch-and-wait policy. This conservative approach is bolstered by a number of observations including the ease with which haematologic control can initially be achieved, the older age of patients with the lymphocytic variant and the paucity of controlled data showing that long disease-free survival or cure can result from the use of aggressive treatment. Given these circumstances, it is not surprising that many such individuals are managed outside specialised centres using a variety of agents and schedules, both of which may, on occasions, be inappropriate. Accumulating evidence suggests a need to reconsider these practices since cure is now possible in selected patients with chronic granulocytic leukaemia while the use of multi-drug regimens in the lymphatic form can significantly improve survival. These advances are the result of carefully conducted clinical trials involving many individuals the world over and constitute the basis fo r advocating early referral to those institutions where all the necessary expertise is available.

  17. CD10 is a marker for cycling cells with propensity to apoptosis in childhood ALL

    OpenAIRE

    G. Cutrona; Tasso, P; Dono, M; Roncella, S; M. ULIVI; Carpaneto, E M; Fontana, V; Comis, M; F. Morabito; Spinelli, M.; Frascella, E.; Boffa, L C; G. Basso; Pistoia, V.; Ferrarini, M.

    2002-01-01

    CD10 constitutes a favourable prognostic marker for childhood acute lymphoblastic leukaemia. Since correlations between CD10, cell cycle and apoptotic abilities were demonstrated in various cell types, we investigated whether differences existed in the cycling/apoptotic abilities of CD10-positive and CD10-negative B acute lymphoblastic leukaemia cells. Twenty-eight cases of childhood acute lymphoblastic leukaemia (mean age of 6.8 years) were subdivided into two groups according to high (17 ca...

  18. Department of Energy's John O'Fallon Begins New Position; Robin Staffin Appointed Acting HEP Director

    CERN Multimedia

    Baggett, N

    2003-01-01

    Officials of the DOE's Office of High Energy and Nuclear Physics have announced that after 15 years as Director of the Division of High Energy Physics, Dr. John R. O'Fallon has accepted the position of Executive Assistant for International and Interagency Planning, in the Office of the Associate Director for High Energy and Nuclear Physics, effective March 24, 2003 (1 page).

  19. Stillwater Wildlife Management Area, Anaho Island National Wildlife Refuge, Fallon National Wildlife Refuge: Refuge Narrative Report: 1977, 1978, 1977

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Stillwater WMA, Anaho Island NWR, and Fallon NWR outlines Refuge accomplishments during the 1977-1979. The report begins with an...

  20. Stillwater Wildlife Management Area, *Anaho Island National Wildlife Refuge and Fallon NWR: Refuge Narrative Report: Calendar Year 1972

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Stillwater WMA, Anaho Island NWR, and Fallon NWR outlines Refuge accomplishments during the 1972 calendar year. The report begins...

  1. Autoimmunity in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Lischner, M; Prokocimer, M; Zolberg, A; Shaklai, M

    1988-08-01

    Seventy-nine patients with chronic lymphocytic leukaemia were evaluated for the presence of autoimmune diseases and autoantibodies. One patient has polymyositis and two additional patients presented with features suggestive of pernicious anaemia and chronic active hepatitis. The Coombs' direct test was positive in 7% and immune thrombocytopenia was present in 8.1% of patients. Five (7%) patients had M-protein in the serum. No increased frequency of other autoantibodies was noted in our study group. We conclude that the propensity to develop antibodies is restricted only to the haematopoietic system and that there is no increased frequency of non-haematological autoimmune diseases in chronic lymphatic leukaemia. PMID:3249703

  2. Breast cancers and leukaemias after irradiation. Cancers du sein et leucemies apres irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Vathaire, F. de (Centre de Lutte Contre le Cancer Gustave-Roussy, 94 - Villejuif (France))

    1994-01-01

    The influence of new data or recent re-analysis concerning the risks of breast cancer and leukaemia after irradiation is summarized in this article. The risk of breast cancer, particularly after irradiation during childhood, seems to be more important than estimated previously. Because the pattern of risk after irradiation seems to be multiplicative and since breast cancer is very frequent among western populations, these new findings may have important consequences in public health. Despite leukaemias have been known for a long time to be a radioinduced tumour, very little information is available about the effects of age at irradiation and dose rate. (author). 9 refs., 2 tabs.

  3. 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.)

  4. A four-point clinical criteria distinguishes immune thrombocytopenia from acute lymphoblastic leukaemia.

    Science.gov (United States)

    Lum, S H; How, S J; Ariffin, H; Krishnan, S

    2016-02-01

    Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage. PMID:27130741

  5. Incidence of leukaemia in young people around the La Hague nuclear waste reprocessing plant: a sensitivity analysis

    International Nuclear Information System (INIS)

    The objectives are to investigate the incidence of childhood leukaemia in young people around the French nuclear waste reprocessing plant (La Hague, Normandy) for the period 1978-1992, and to check the sensitivity of the results to the choice of disease clustering tests and reference rates. The performance of three statistical procedures are compared: a conventional approach; a Poisson maximum test, and an extraction mapping technique. The results are in general agreement and demonstrate the apparent existence of a distinct cluster of childhood leukaemia, contiguous and south-east of the La Hague nuclear facility. (author)

  6. Genetic variegation of clonal architecture and propagating cells in leukaemia.

    Science.gov (United States)

    Anderson, Kristina; Lutz, Christoph; van Delft, Frederik W; Bateman, Caroline M; Guo, Yanping; Colman, Susan M; Kempski, Helena; Moorman, Anthony V; Titley, Ian; Swansbury, John; Kearney, Lyndal; Enver, Tariq; Greaves, Mel

    2011-01-20

    Little is known of the genetic architecture of cancer at the subclonal and single-cell level or in the cells responsible for cancer clone maintenance and propagation. Here we have examined this issue in childhood acute lymphoblastic leukaemia in which the ETV6-RUNX1 gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or 'driver' copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of subclones identified and a composite picture of subclonal architecture and putative ancestral trees assembled. Subclones in acute lymphoblastic leukaemia have variegated genetics and complex, nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukaemia propagating cells, assayed by serial transplantation in NOD/SCID IL2Rγ(null) mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. These data have implications for cancer genomics and for the targeted therapy of cancer. PMID:21160474

  7. Control of feline leukaemia virus.

    NARCIS (Netherlands)

    K. Weijer (Kees); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Ab)

    1989-01-01

    textabstractFeline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS (

  8. An analysis of leukaemia, lymphoma and other malignancies together with certain categories of non-cancer mortality in the first generation offspring (F1) of the Japanese bomb survivors

    International Nuclear Information System (INIS)

    The absence of any significant excess of childhood leukaemia in the offspring of the Japanese bomb survivors has provided strong evidence against a causal interpretation of the association between paternal preconception radiation dose and the incidence of childhood leukaemia in the offspring of employees at the Sellafield nuclear installation, West Cumbria. The use of the Japanese data has, however, been questioned on the basis that leukaemia cases may have been under-recorded in the years immediately following the bombings. In order to investigate possible misdiagnoses of leukaemia cases in the first generation offspring (F1) of the Japanese bomb survivors, analyses have been undertaken of cases of leukaemia, non-Hodgkin's lymphoma (NHL), and all other malignancies, together with deaths due to blood diseases, deaths due to infectious diseases and deaths from unknown causes. (author)

  9. Autoimmunity in chronic lymphocytic leukaemia.

    OpenAIRE

    Lischner, M.; Prokocimer, M.; Zolberg, A.; Shaklai, M.

    1988-01-01

    Seventy-nine patients with chronic lymphocytic leukaemia were evaluated for the presence of autoimmune diseases and autoantibodies. One patient has polymyositis and two additional patients presented with features suggestive of pernicious anaemia and chronic active hepatitis. The Coombs' direct test was positive in 7% and immune thrombocytopenia was present in 8.1% of patients. Five (7%) patients had M-protein in the serum. No increased frequency of other autoantibodies was noted in our study ...

  10. Dexamethasone in the maintenance phase of acute lymphoblastic leukaemia treatment: is the risk of lethal infections too high?

    NARCIS (Netherlands)

    Poele, E.M. Te; Bont, E.S. de; Boezen, H.M.; Revesz, T.; Bokkerink, J.P.M.; Beishuizen, A.; Nijhuis, I.J.M.; Oude Nijhuis, C.S.; Veerman, A.J.P.; Kamps, W.A.

    2007-01-01

    We report an increased incidence of infectious deaths during maintenance treatment of the ninth protocol for acute lymphoblastic leukaemia of the Dutch Childhood Oncology Group (DCOG-ALL-9). The main difference in maintenance treatment between DCOG-ALL-9 and the DCOG-ALL-7 and DCOG-ALL-8 protocols i

  11. Dexamethasone in the maintenance phase of acute lymphoblastic leukaemia treatment : Is the risk of lethal infections too high?

    NARCIS (Netherlands)

    Te Poele, Esther M; de Bont, Eveline S J M; Boezen, Hendrika; Revesz, Tom; Bökkerink, Jos P M; Beishuizen, Auke; Nijhuis, Ilse J M; Oude Nijhuis, Claudi S M; Veerman, Anjo J P; Kamps, Willem A

    2007-01-01

    We report an increased incidence of infectious deaths during maintenance treatment of the ninth protocol for acute lymphoblastic leukaemia of the Dutch Childhood Oncology Group (DCOG-ALL-9). The main difference in maintenance treatment between DCCG-ALL-9 and the DCOG-ALL-7 and DCOG-ALL-8 protocols i

  12. Vincristine induced apoptosis in acute lymphoblastic leukaemia cells: A mitochondrial controlled pathway regulated by reactive oxygen species?

    NARCIS (Netherlands)

    Groninger, E.; Boer, A.W. de; Graaf, S.S.N. de; Kamps, W.A.; Bont, E.S. de

    2002-01-01

    Vincristine (VCR), a microtubule interfering anti-cancer agent, plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL). The route of VCR induced apoptosis in ALL cells is not well defined. In this study we demonstrated caspase-9 and -3 activation in vivo in bone marrow le

  13. Summary curves for patients transplanted for chronic myeloid leukaemia salvaged by a donor lymphocyte infusion: the current leukaemia-free survival curve

    DEFF Research Database (Denmark)

    Klein, John P.; Keiding, Niels; Shu, Youyi;

    2000-01-01

    CML, donor lymphocyte infusion, leukaemia-free survival, current leukaemia-free survival, statistical methods......CML, donor lymphocyte infusion, leukaemia-free survival, current leukaemia-free survival, statistical methods...

  14. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2016-03-01

    Full Text Available Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.

  15. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    OpenAIRE

    Avcu, Gulhadiye; Karapinar, Deniz Yilmaz; Yazici, Pinar; Duyu, Muhterem; Polat, Suleyha Hilmioglu; Atabay, Berna; Doganavsargil, Basak; Karapinar, Bulent

    2016-01-01

    Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immun...

  16. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot study

    DEFF Research Database (Denmark)

    Frandsen, Thomas L; Abrahamsson, Jonas; Lausen, Birgitte;

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m(2), ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  17. Occupational exposure of fathers to ionizing radiation and the risk of leukaemia in offspring

    International Nuclear Information System (INIS)

    An epidemiologic study was performed to determine whether there was an association between childhood leukaemia and the occupational exposure of fathers in the nuclear industry to ionizing radiation prior to the child's conception. The study employed a case-control design. Children with cancer ('cases') and children who did not develop cancer ('controls') were compared with respect to their exposure history. The cases, which occurred from 1950 to 1988, consisted of children aged 0 to 14 years who died from or were diagnosed with leukaemia and were born to mothers who lived near an operating nuclear facility in Ontario. Eight controls were matched to each case according to date of birth and mother's residence. There were 112 cases and 890 controls (six controls died before the development of the associated case's leukaemia). Data on the occupational exposure of the 1002 fathers were obtained from the Canadian National Dose Registry (NDR) and examination of employer records. Links to the NDR were found for 95 fathers. For each father doses were obtained regarding whole body external dose, tritium dose, and (for uranium miners) internal exposures to the lungs due to radon and radon daughters. Radiation exposures were estimated (a) over the father's lifetime before the child's conception; (b) during the six months prior to the child's conception; (c) during the three months prior to the child's conception; and (d) over the father's lifetime, ending in the month of the child's diagnosis. There was no evidence of an elevated leukaemia risk in relation to any exposure period or exposure type, and there was no apparent gradient of effect with increasing radiation dose. It is concluded that there was no association between childhood leukaemia and the occupational exposure of fathers to ionizing radiation prior to conception or diagnosis. Odds ratios were close to 1.0 for all radiation dose categories and occupations except for uranium mining, which had a larger but not

  18. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria.

    OpenAIRE

    Gardner, M. J.; Snee, M P; Hall, A J; Powell, C A; Downes, S; Terrell, J D

    1990-01-01

    OBJECTIVE--To examine whether the observed excess of childhood leukaemia and lymphoma near the Sellafield nuclear plant is associated with established risk factors or with factors related to the plant. DESIGN--A case-control study. SETTING--West Cumbria health district. SUBJECTS--52 Cases of leukaemia, 22 of non-Hodgkin's lymphoma, and 23 of Hodgkin's disease occurring in people born in the area and diagnosed there in 1950-85 under the age of 25 and 1001 controls matched for sex and date of b...

  19. Leukaemia incidence after iodine-131 exposure

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Per (Karolinska Hospital, Stockholm (Sweden). Dept. of General Oncology); Boice, J.D. Jr. (National Cancer Inst., Bethesda, MD (United States). Div. of Cancer Etiology); Berg, Gertrud (Sahlgren' s Hospital, Gothenburg (Sweden). Dept. of General Oncology) (and others)

    1992-07-04

    Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46 988 Swedish patients exposed to iodine-131 ([sup 131]I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy. 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09. Similar increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from [sup 131]I. One reason for the absence of a radiation effect includes the possible lowering of risk when exposure is protracted over time as occurs with [sup 131]I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to [sup 131]I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident. (Author).

  20. Evaluation of management options for disposal of salt and trace element laden agricultural drainage water from the Fallon Indian Reservation, Fallon, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Tokunaga, Tetsu; Benson, S.

    1991-03-01

    This is the final report describing work performed on the Fallon Indian Reservation by the Earth Sciences Division at Lawrence Berkeley Laboratory during FY90. These investigations were initiated at the request of the United States Bureau of Reclamation in response to recent concerns regarding disposal of agriculture drainage water from the Reservation. The Reservation is transected by numerous irrigation and drainage canals, including the TJ Drain. Recent investigations by the US Fish and Wildlife Service have demonstrated that water in the TJ Drain is toxic to several aquatic indicator organisms, including bluegills, fathead minnows and daphnids. This information, coupled with recent die-offs of fish and birds, has lead to concern about continued discharge of TJ Drain water into local surface waters. In late 1990, plans for closing the TJ Drain and providing for alternative drainage were initiated. We aim to provide information for assessing options fro disposal of agricultural drainage water from the Reservation. In particular, our studies focuses on irrigation and drainage of lands currently serviced by the TJ Drain. Options for continued irrigation and drainage of the Reservation fall broadly into two categories: options that provide an alternative to drain water disposal into the SWMA; and options that include continuing the current practice of drain water disposal into the SWMA. Other options include elements of both of these alternatives. Additional discussion of specific options will follow a brief summary of the technical work supporting our assessment of drainage related issues at the Reservation. 67 refs., 57 figs., 15 tabs.

  1. Stillwater National Wildlife Refuge including Stillwater Wildlife Management Area, Fallon National Wildlife Refuge, and Anaho Island National Wildlife Refuge: Annual narrative report: Calendar year 1991

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Stillwater NWR and WMA, Fallon NWR, and Anaho Island NWR outlines Refuge accomplishments during the 1991 calendar year. The report...

  2. Stillwater National Wildlife Refuge including Stillwater Wildlife Management Area, Fallon National Wildlife Refuge, and Anaho Island National Wildlife Refuge: Annual narrative report: Calendar year 1992

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Stillwater NWR and WMA, Fallon NWR, and Anaho Island NWR outlines Refuge accomplishments during the 1992 calendar year. The report...

  3. Stillwater National Wildlife Refuge, Stillwater Wildlife Management Area, Anaho Island National Wildlife Refuge and Fallon National Wildlife Refuge: Narrative Report: 1965

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Fallon, Stillwater and Anaho Island National Wildlife Refuges are located in northwest Nevada and are administered by the refuge administrative office in...

  4. Stillwater National Wildlife Refuge, Stillwater Wildlife Management Area, Anaho Island National Wildlife Refuge and Fallon National Wildlife Refuge: Narrative Report: 1964

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Fallon, Stillwater and Anaho Island National Wildlife Refuges are located in northwest Nevada and are administered by the refuge administrative office in...

  5. Stillwater National Wildlife Refuge, Stillwater Wildlife Management Area, Anaho Island National Wildlife Refuge and Fallon National Wildlife Refuge: Narrative Report: 1966

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Fallon, Stillwater and Anaho Island National Wildlife Refuges are located in northwest Nevada and are administered by the refuge administrative office in...

  6. Stillwater National Wildlife Refuge including Stillwater Wildlife Management Area, Fallon National Wildlife Refuge, and Anaho Island National Wildlife Refuge: Annual narrative report: Calendar year 1990

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Stillwater NWR and WMA, Fallon NWR, and Anaho Island NWR outlines Refuge accomplishments during the 1990 calendar year. The report...

  7. Stillwater National Wildlife Refuge, Stillwater Wildlife Management Area, Anaho Island National Wildlife Refuge and Fallon National Wildlife Refuge: Narrative Report: 1967

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Fallon, Stillwater and Anaho Island National Wildlife Refuges are located in northwest Nevada and are administered by the refuge administrative office in...

  8. Gene expression profiling in acute myeloid leukaemia

    NARCIS (Netherlands)

    de Jonge, H. J. M.; Huls, G.; de Bont, E. S. J. M.

    2011-01-01

    Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by clonal malignant haematopoiesis with a differentiation arrest and excessive proliferation of leukaemic blasts. Over the past decades, the heterogeneity of AML has been illustrated by evolving classifications based on morpholog

  9. Hospitalisation for infection prior to diagnosis of acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Vestergaard, Therese Risom; Rostgaard, Klaus; Grau, Katrine;

    2013-01-01

    BACKGROUND: It has been proposed that infections in infancy and early childhood are associated with a reduced risk of childhood acute lymphoblastic leukaemia (ALL). We tested this hypothesis in a register-based study of hospitalisations for infectious diseases prior to diagnosis of childhood ALL....... PROCEDURE: A nation-wide cohort encompassing all Danish children aged 0-14 years and born between 1977 and 2008 (N = 1,778,129) was established and followed for hospitalisations for infectious diseases and risk of childhood ALL. The exposure was lagged 1 year to limit reverse causality. In the statistical...... hospitalisations for infectious diseases before (incidence rate ratio = 0.92, 95% confidence interval 0.78-1.07) nor at/after 2 years of age (incidence rate ratio = 1.04, 95% confidence interval 0.81-1.32). This also applied to subsets of ALL supposedly initiated prenatally. CONCLUSION: The absence of association...

  10. Host, family and community proxies for infections potentially associated with leukaemia

    International Nuclear Information System (INIS)

    Three hypotheses have proposed the involvement of infections in the aetiology of childhood leukaemia, suggesting either a specific leukemogenic infection or a series of common infections that lead to a dys-regulation of the immune system. Much of the evidence for the link with infections has been based on epidemiological observations, often using proxy measures of infection. Proxy measures include population mixing, parental occupation, age distribution of incidence, spatial and space-time clustering of cases, birth order and day care during infancy. This paper discusses the proxies used and examines to what extent a commonly used proxy measure, birth order, is a fair representation of either specific infections or general infectious load. It is clear that although leukaemia, and other diseases, may be linked with infections, one needs to (1) measure specific and general infections with more accuracy and (2) understand how proxy measures relate to real infections in the population. (authors)

  11. Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history-adjusted marginal structural models

    DEFF Research Database (Denmark)

    Rosthøj, Susanne; Keiding, Niels; Schmiegelow, Kjeld

    2012-01-01

    Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment...... of the methods in relation to the formulation of alternative dosing strategies for the maintenance therapy....

  12. Biphenotypic acute leukaemia: Case reports of two paediatric patients

    Directory of Open Access Journals (Sweden)

    Vujić Dragana

    2010-01-01

    Full Text Available Introduction. Biphenotypic acute leukaemia is an uncommon type of leukaemia whose blasts co-express myeloid and B-or T-lymphoid antigens. Case report. We describe two cases of paediatric patients with biphenotypic acute leukaemia. A four-year-old female patient was found to have myeloid and B-lymphoid associated antigens in the same blast cells. Cytogenetic analysis showed a Philadelphia (Ph positivity t (9;22 (q34;q11 with rearrangements of M.bcr-Abl (p210. She was treated with combined acute myeloid leukaemia/acute lymphoblastic leukaemia induction therapy followed by autologous stem cell transplantation. The patient died due to the complications of stem cell transplantation procedure. Another patient was a 20-month-old girl with myeloid and T-lymphoid associated antigens in the blast cells and with normal karyotype. She received acute myeloid leukaemia induction therapy. She has never achieved remission. Discussion. Immunophenotype is essential to establish the diagnosis of biphenotypic acute leukaemia according to the scoring system adopted by the European Group of Immunological Classification of Leukaemia. There is no agreement about uniformity in treatment for the patients with this type of leukaemia. Biphenotypic acute leukaemia is a high risk leukaemia which requires a more intensive treatment. Conclusion. Therapy for every patient with biphenotypic acute leukaemia should depend on their immunophenotype and gene rearrangement profiles.

  13. Long-term therapy related side effect on endocrine system among survivor with paediatric brain tumour and acute lymphoblastic leukaemia

    OpenAIRE

    Chan, Shu-wing, Sophia; 陳舒穎

    2015-01-01

    Background: Acute lymphoblastic leukaemia (ALL) and brain tumours are frequently seen in childhood malignancies. With the improved effectiveness of treatments, approximately 70–80% patients can be cured of their primary illness. However, therapy-related long-term sequelae among survivors are becoming a major concern. Traditional treatments include surgery, radiation and chemotherapy, and these have been shown to have prolonged side effects on the endocrine system, and symptoms may develop mon...

  14. Acute leukaemia: making sense of a complex blood cancer.

    LENUS (Irish Health Repository)

    Meenaghan, Teresa

    2012-01-01

    Acute leukaemia represents a diverse group of blood cancers that affect both children and adults. Treatment schedules for these haematology cancers are often prolonged, with many associated side effects and complications. Nurses caring for patients with acute leukaemia require an anticipatory approach, where care is aimed at minimizing the side effects of treatment and being constantly vigilant for any impending adverse effects. Moreover, patients require support for the psychosocial issues that can arise for patients during their illness. This article provides an overview of acute lymphoblastic leukaemia and acute myeloid leukaemia. Nursing considerations in the care of patients being treated for acute leukaemia are also explored.

  15. Case-control study of leukaemia and non-Hodgkin's lymphoma in children in Caithness near the Dounreay nuclear installation

    International Nuclear Information System (INIS)

    A case-control study was performed to examine whether the observed excess of childhood leukaemia and non-Hodgkin's lymphoma in the area around the Dounreay nuclear installation is associated with established risk factors, or with factors related to the plant, or with parental occupation in the nuclear industry. No raised relative risks were found for prenatal exposure to X-rays, social class of parents, employment at Dounreay before conception or diagnosis, father's dose of ionising radiation before conception, or child's residence within 50 m of the path of microwave transmission beams. Results also proved negative for all lifestyle factors except an apparent association with use of beaches within 25 km of Dounreay. However, this result was based on small numbers, arose in the context of multiple hypothesis testing, and is certainly vulnerable to possible systematic bias. It was concluded that the raised incidence of childhood leukaemia and non-Hodgkin's lymphoma around Dounreay cannot be explained by paternal occupation at Dounreay or by paternal exposure to external ionising radiation before conception. The observation of an apparent association between the use of beaches around Dounreay and the development of childhood leukaemia and non-Hodgkin's lymphoma might be an artefact of multiple testing and influenced by recall bias. (author)

  16. Case-control study on risk factors for leukaemia and brain tumours in children under 5 years in Germany.

    Science.gov (United States)

    Spix, C; Schulze-Rath, R; Kaatsch, P; Blettner, M

    2009-01-01

    In the context of a case control study on the cancer risk for children under five by distance to the nearest nuclear power plant, we collected information on other risk factors in a subset. We present the interview study as if it had been an independent study. Parents of 471 cases with Leukaemia, Lymphoma or CNS (Central Nervous System)-tumour from the German Childhood Cancer Registry, diagnosed at age under 5 in the years 1993-2003, and 1,457 matched controls were to be interviewed. For Leukaemia, 243 cases/604 controls, and for CNS 102 cases/246 controls participated, lymphoma cases were too few. Questions related to social status, ionizing radiation, pregnancy and birth, immune system, and selected toxins. The analysis is exploratory in nature; variables were selected by backward elimination. For leukaemia we found a significant protective effect of social contacts (OR=0.50, 95% CI [0.29;0.87]) and a risk for high birth weight (OR=1.96 95% CI [1.12;3.41] comparing >4,000 g to "normal"). We could not reproduce other associations reported in the literature such as a negative association with allergies. For CNS tumours we found a significant protective effect of social contacts (OR=0.30 95% CI [0.13;0.72]), of pesticides and herbicides (OR=0.39 95% CI [0.18;0.83]) and an increased risk for low birth weight (p=0.0232). This study on risk factors for childhood leukaemia and brain tumours is relatively small and exploratory. We could reproduce some major associations reported in the literature (leukaemia: social contacts and high birth weight) but not others. Some observations may be reporting artefacts or self selection artefacts. PMID:19890788

  17. Hydrologic, lithologic, and chemical data for sediment in the shallow alluvial aquifer at two sites near Fallon, Churchill County, Nevada, 1984-85

    Science.gov (United States)

    Lico, M.S.; Welch, A.H.; Hughes, J.L.

    1986-01-01

    The U.S. Geological Survey collected an extensive amount of hydrogeologic data from the shallow alluvial aquifer at two study sites near Fallon, Nevada, from 1984 though 1985. These data were collected as part of a study to determine the geochemical controls on the mobility of arsenic and other trace elements in shallow groundwater systems. The main study area is approximately 7 miles south of Fallon. A subsidiary study area is about 8 miles east of Fallon. The data collected include lithologic logs and water level altitudes for the augered sampling wells and piezometers, and determinations of arsenic and selenium content, grain size, porosity, hydraulic conductivity, and mineralogy for sediment samples from cores. (USGS)

  18. Water-level changes and directions of ground-water flow in the shallow aquifer, Fallon area, Churchill County, Nevada

    Science.gov (United States)

    Seiler, R.L.; Allander, K.K.

    1993-01-01

    The Truckee-Carson-Pyramid Lake Water Rights Settlement Act of 1990 directed the U.S. Fish and Wildlife Service to acquire water rights for wetland areas in the Carson Desert, Nevada. The public is concerned that htis acquisition of water rights and delivery of the water directly to wildlife areas would result in less recharge to the shallow ground water in the Fallon area and cause domestic wells to go dry. In January 1992, the U.S. Geological Survey, in cooperation with U.S. Fish and Wildlife Service, began a study of the shallow ground-water system in the Fallon area in Churchill County, Nevada. A network of 126 wells in the study area was monitored. Between January and November 1992, water levels in most wells declined, usually less than 2 feet. The maximum measured decline over this period was 2.68 feet in a well near Stillwater Marsh. Between April and July, however, water levels rose in irrigated areas, typically 1 to 2 feet. Newlands Project water deliveries to the study area began soon after the turn of the century. Since then, water levels have risen more than 15 feet across much of the study area. Water lost from unlined irrigtiaon canals caused the stage in Big Soda Lake to rise nearly 60 feet; ground-water levels near the lake have risen 30 to 40 feet. The depth to water in most irrigated areas is now less than 10 feet. The altitude of the water table ranges from 4.025 feet above sea level 11 miles west of Fallon to 3,865 feet in the Stillwater Marsh area. Ground water flows eastward and divides; some flow goes to the northeast toward the Carson Sink and Stillwater areas, and some goes southeastward to Carson Lake.

  19. Leukaemia and lymphoma among Czech uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Tomasek, L.; Malatova, I. [National Radiation Protection Institute, Prague (Czech Republic)

    2006-07-01

    Leukaemia is one of the most sensitive cancers in relation to ionizing radiation. It is surprising that in studies of uranium miners, no risk of leukaemia in relation to cumulated radon exposure was observed (Darby et al, 1995). However, when the risk among Czech uranium miners was analyzed in dependence on duration of exposure, the trend was significant. These results were based on 10 cases (Tomasek, 1993). Since then the original cohort of 4320 miners has been extended by another cohort, now including nearly 10 000 uranium miners and the follow-up is longer by 10 years. The present report aims to analyze the risk of haemopoietic cancers in the Czech cohort accounting for both external and internal doses, similarly as reported by Jacobi and Roth (1995), and using available data on metal content and airborne particulates for dose estimates.The present results of follow-up show that increased risk of leukaemia among uranium miners is significantly associated with cumulated equivalent red bone marrow doses which is dominated by exposures to long lived alpha radionuclides in airborne particulates. The increased mortality is mainly observed decades after exposure and is consistent with estimated internal dose to red bone marrow. The estimated risk coefficient for leukaemia is consistent with results from other studies, however, further studies are needed to reduce uncertainty in the risk estimates. (N.C.)

  20. An algorithm for leukaemia immunophenotype pattern recognition.

    Science.gov (United States)

    Petrovecki, M; Marusić, M; Dezelić, G

    1993-01-01

    Since leukaemia-specific leucocyte antigen has not been identified to date, the immunological diagnosis of leukaemia is achieved through the application of a wide set of monoclonal antibodies specific for surface markers on leukaemic cells. Thus, the interpretation of leukaemia immunophenotype seems to be a mathematically determined comparison of 'what we found' and 'what we know' about it. The objective of this study was to establish an algorithm for transformation of empirical rules into mathematical values to achieve proper decisions. Recognition of leukaemia phenotype was performed by comparison of phenotyping data with reference data, followed by scoring of such comparisons. Systematic scoring resulted in the formation of new numerical variables allocated to each state, whereas a most significant variable was described as a complex measure of compatibility. A system of recognized states was described by mathematical variables measuring the confidence of information systems, i.e. maximal, total and relative entropy. The entire algorithm was derived by matrix algebra and coded in a high-level program language. The list of the states recognized appeared to be especially helpful in differential diagnosis, occasionally pointing to states that had not been in the scientist's mind at the start of the analysis. PMID:8366688

  1. Seismic reflection exploration of geothermal reservoir at Naval Air Station (NAS) Fallon, Nevada

    Science.gov (United States)

    Alay G., Gebregiorgis

    The Primary objective of this study is to increase geologic and tectonic understanding of the geothermal resources at the Naval Air Station (NAS) Fallon, Nevada. The seismic reflection method is employed to study faults, fractures and other tectonic structures in the subsurface in order to identify geothermal drill targets. The efficiency of geothermal systems is strongly dependent on water circulation. Discrete faults may be permeable and provide pathways for water flow depending on the fracture density. It is therefore desirable to detect and map faults and fracture zones and characterize their physical properties when evaluating a geothermal prospect. The seismic data for this project were provided by the NAS environmental research program in Ridgecrest, CA. However, the data collection information was not available so the work includes determining the line geometry and mapping shot points to field files in order to process the data. ProMAX 2D(TM) is the software used to determine the geometry and to process the data. Data processing includes eliminating noise, datum and refraction statics, trace muting, bandpass filter, automatic gain control, amplitude recovery, CMP sorting, velocity analysis and NMO correction, stacking and migration. The results of this study indicate the presence of thick basin fill including Tertiary and Quaternary sediments underlain by Tertiary basalts which are interpreted to be capping rocks for the geothermal reservoirs. This seismic reflection study also reveals the presence of strongly fractured pre-Tertiary basement complex with their top at about 1500m on the north and west and about 900 m on the eastern and southern part of the study area.

  2. Leukaemia in the vicinity of nuclear installations - a review; Leukaemiehaeufigkeit in der Umgebung kerntechnischer Anlagen - eine Uebersicht

    Energy Technology Data Exchange (ETDEWEB)

    Grosche, B. [Bundesamt fuer Strahlenschutz, Aussenstelle Oberschleissheim, Fachbereich Strahlung und Gesundheit, Oberschleissheim (Germany)

    2006-07-01

    Based on the finding of an increased leukaemia risk among young people (aged 0-24) in the small village of Seascale, south of the Sellafield reprocessing plant, a discussion started on whether there is in general an elevated number of leukaemia cases to be observed in the vicinity of nuclear power plants. An overview on existing findings leads to the conclusion that this is not the case among adults. Among children and juveniles, a slight increase can be observed, which is most pronounced among the youngest age groups in the nearest vicinity of the plants. Estimates of radiation exposures to the public make a causal relationship between the radioactive discharges and the cases implausible. Other explanations are discussed, namely that population influx into a relatively sparsely populated area, e.g. due to new industry settlements, might lead to an altered infection situation in the respective area which than causes an increased leukaemia rate. Recent results are indicative for a causative role of infections in relation to childhood leukaemias. This explanation is opposed by the finding, that elevated rates have also been observed around potential nuclear sites where there was no population influx. Overall, current findings have to be considered as not fully understood. (orig.)

  3. A comparison of the risks of leukaemia and non-Hodgkin's lymphoma in the first generation offspring (F1) of the Danish Thorotrast patients with those observed in other studies of parental pre-conception irradiation

    International Nuclear Information System (INIS)

    The high doses of alpha-particle radiation which Thorotrast delivers to the testes makes the study of offspring of patients, who were administered this diagnostic contrast medium, particularly relevant to the controversy regarding childhood leukaemia in the offspring of the male Sellafield workforce, as it has been suggested that the alpha-particle dose from actinides may, in part, account for the observed association between paternal pre-conception external irradiation and leukaemia. The risks of childhood leukaemia and non-Hodgkin's lymphona found among the offspring of the male Danish cohort of neurosurgical patients injected with Thorotrast for cerebral arteriography are compared with those observed in the offspring of the Sellafield (western Cumbria), Ontario and Scottish radiation workers and in the offspring of the Japanese atomic bomb survivors. Risks are compared using linear and exponential forms of a relative risk model. (author)

  4. Childhood cancer and nuclear power plants in Switzerland: a census-based cohort study

    OpenAIRE

    Spycher, Ben D.; Feller, Martin; Zwahlen, Marcel; Röösli, Martin; von der Weid, Nicolas X.; Hengartner, Heinz; Egger, Matthias; Kuehni, Claudia E.

    2011-01-01

    BACKGROUND: Previous studies on childhood cancer and nuclear power plants (NPPs) produced conflicting results. We used a cohort approach to examine whether residence near NPPs was associated with leukaemia or any childhood cancer in Switzerland. METHODS: We computed person-years at risk for children aged 0-15 years born in Switzerland from 1985 to 2009, based on the Swiss censuses 1990 and 2000 and identified cancer cases from the Swiss Childhood Cancer Registry. We geo-coded place...

  5. Leukoencephalopathy after prophylactic radiation for leukaemia in ataxia telangiectasia.

    OpenAIRE

    Eyre, J A; Gardner-Medwin, D; Summerfield, G P

    1988-01-01

    Children with ataxia telangiectasia have a high probability of developing acute lymphoblastic leukaemia, and have increased sensitivity to chemotherapy and irradiation. We report a 51/2 year old boy who had undiagnosed ataxia telangiectasia when he presented with acute lymphoblastic leukaemia. He subsequently developed a chemoradiation induced leukoencephalopathy after conventional central nervous system prophylaxis.

  6. Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Trněný Marek

    2011-10-01

    Full Text Available Abstract Background The current situation in the treatment of chronic myeloid leukaemia (CML presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment. Methods Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data. Results The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter. Conclusions Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in

  7. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects...... genes and genetic signatures and for reducing dimensionally of gene expression data. Next, we have used machine-learning methods to predict survival and to assess important predictors based on these results. General application of a number of these methods has been implemented into two public query...

  8. Trace elements in scalp hair of leukaemia patients

    OpenAIRE

    Khuder Ali; Bakir Mohammad Adel; Hasan Reem; Mohammad Ali; Habil Khozama

    2014-01-01

    The aim of this study was to determine the concentration of Fe, Ni, Cu, Zn and Pb in scalp hair of leukaemia patients and healthy volunteers, using the optimised XRF method. Leukaemia hair samples were classifi ed corresponding to type, growth and age of the participants. The results showed that the studied trace elements (TEs) in both of leukaemia and control groups were positively skewed. In comparison with the control group, lower Fe, Cu, Zn and Pb and higher of Ni medians were found in al...

  9. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B;

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....... significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated...

  10. Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol

    DEFF Research Database (Denmark)

    Raja, Raheel A; Schmiegelow, Kjeld; Albertsen, BK;

    2014-01-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis...... within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO...... with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1-13), and 11 d (median) from the latest administration of PEG-Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve...

  11. Unilateral parotid gland swelling as the sole presenting symptom of acute lymphoblastic leukaemia in children

    Directory of Open Access Journals (Sweden)

    Yatiee Swany Lahuri

    2015-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL in infants below 1 year of age contributed 2.5–5% of childhood ALL incidence. Children with ALL commonly presented with fever, bruising, mucosal bleeding, bone pain, pallor, hepatosplenomegaly, and lymphadenopathy. Common extra medullary leukaemic infiltration has also been reported at diagnosis of ALL to sites such as the liver, spleen, lymph nodes, brain, testes and even nephromegaly. However ALL presented with parotid infiltration is exceedingly rare. We herein present a case of unilateral parotid enlargement in a child with newly diagnosed ALL. This unusual presentation focuses on the importance of considering ALL in the differential diagnosis of parotid enlargement especially when associated with abnormal blood counts.

  12. Trace elements in scalp hair of leukaemia patients

    Directory of Open Access Journals (Sweden)

    Khuder Ali

    2014-08-01

    Full Text Available The aim of this study was to determine the concentration of Fe, Ni, Cu, Zn and Pb in scalp hair of leukaemia patients and healthy volunteers, using the optimised XRF method. Leukaemia hair samples were classifi ed corresponding to type, growth and age of the participants. The results showed that the studied trace elements (TEs in both of leukaemia and control groups were positively skewed. In comparison with the control group, lower Fe, Cu, Zn and Pb and higher of Ni medians were found in all studied leukaemia patients. The median rank obtained by Mann-Whitney U-test revealed insignifi cant differences between the leukaemia patients subgroups and the controls. An exact probability (α 0.70 in the scalp hair of control group were observed between Ni/Fe-Ni, Cu/Fe-Cu, Zn/Fe-Zn, Pb/Fe-Pb, Cu/Ni-Zn/Ni, Cu/Ni-Pb/Ni, Zn/Ni-Pb/Ni, Zn/Fe-Zn/Cu, Pb/Ni-Ni and Ni/Fe-Pb/Ni, whereas only very strong positive ratios in the scalp hair of leukaemia patients group were observed between Ni/Fe-Ni, Cu/Fe-Cu, Zn/Fe-Zn and Pb/Fe-Pb, all correlations were signifi cant at p < 0.05. Other strong and signifi cant correlations were also observed in scalp hair of both groups. Signifi cant differences between grouping of studied TEs in all classifi ed leukaemia groups and controls were found using principal component analysis (PCA. The results of PCA confi rmed that the type and the growth of leukaemia factors were more important in element loading than the age factor.

  13. Case-control study of leukaemia among young people near La Hague nuclear reprocessing plant: the environmental hypothesis revisited

    International Nuclear Information System (INIS)

    OBJECTIVE: To investigate the association between childhood leukaemia and established risk factors or other factors related to La Hague nuclear waste reprocessing plant. DESIGN: Case-control study. SETTING: Area within a 35 km radius of La Hague, Normandy, France. SUBJECTS: Twenty seven cases of leukaemia diagnosed during the period 1978-93 in people aged under 25 years and 192 controls matched for sex, age, place of birth, and residence at time of diagnosis. MAIN OUTCOME MEASURES: Antenatal and postnatal exposure to x rays and viral infections, occupational exposure of parents (particularly ionising radiation), living conditions, lifestyle of parents and children. RESULTS: Increased trends were found for use of local beaches by mothers and children (P < or = 0.01); relative risks 2.87 (95% confidence intervals 1.05 to 8.72) and 4.49 (1.52 to 15.23) when categories were aggregated in two levels (more or less than once a month). Consumption of local fish and shellfish also showed an increased trend (P 0.01); relative risk 2.66 (0.91 to 9.51) when categories were grouped in two levels (more or less than once a week). A relative risk of 1.18 a year (1.03 to 1.42) was observed for length of residence in a granite-built house or in a granitic area. No association was shown with occupational radiation exposure in parents. CONCLUSIONS: There is some convincing evidence in childhood leukaemia of a causal role for environmental radiation exposure from recreational activities on beaches. New methods for identifying the environmental pathways, focusing on marine ecosystems, are warranted

  14. Distribution of HLA antigens in families of patients with leukaemias

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2008-01-01

    Full Text Available Introduction. Since the discovery of major histocompatihility complex influence on manse leukaemia in 1964, an HLA association with leukaemia in humans has been considered as a possible genetic risk factor that contributes to development of leukaemia. In addition to associations of several IILA antigens with leukaemias, it has been observed that patients with leukaemia have an increase in the frequency of HLA identical siblings, higher degree of HLA compatibility with their parents as well as higher parental HLA sharing rate in comparison to the families without patients suffering from leukaemia. Material and methods. To test hypothesis that susceptibility to leukaemia can be caused bv influence of a recessive genes associated with the major histocompatibilily complex in man, we analyzed the distribution of I class HLA antigens in 77 families of patients suffering from different types of leukaemia. In the affected families and in 72 families of healthy controls, we investigated HLA identical sibling frequency, parental sharing of one, two or three HLA antigens and degree of compatibility of parents and off springs: existence of haploidentity, compatibility in l' and 4/4 HLA antigens of A and B loci. Results We have found that in families with affected persons there is a statistically significant difference in number of HLA identical siblings in comparison to the group of healthy controls (t=2,63. Also the results have shown that among the parents of affected persons there is a statistically significant difference in mutual compatibility in one (t=3,012 and two ft= 2,4 HLA antigens. In addition, we observed an increase in the frequency of higher rate of compatibility between patients and their parents (t=3,88 in l' HLA antigens, to their mothers (t=2,83 and to their fathers (t=2,55, respectively, in comparison to the healthy control group. Conclusion The results of this study show that in families with persons suffering from leukaemia there are

  15. Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia

    NARCIS (Netherlands)

    Meijers, JCM; Oudijk, EJD; Mosnier, LO; Nieuwenhuis, HK; Fijnheer, R; Bouma, Bonno N.; Bos, R

    2000-01-01

    Acute promyelocytic leukaemia (APL) is a disease that is distinguished from other leukaemias by the high potential for early haemorrhagic death. Several processes are involved, such as disseminated intravascular coagulation and hyperfibrinolysis. Recently, TAFI (thrombin-activatable fibrinolysis inh

  16. Gastrointestinal bleeding due to large bowel infiltration by chronic lymphocytic leukaemia.

    OpenAIRE

    Tucker, J.; Cachia, P. G.

    1986-01-01

    A 66 year old woman with a 9 year history of chronic lymphocytic leukaemia developed intermittent rectal bleeding for 9 months; sigmoidoscopic biopsy proved that this was due to large bowel infiltration by leukaemia. This is a very rare occurrence.

  17. Managing children with chronic myeloid leukaemia (CML): recommendations for the management of CML in children and young people up to the age of 18 years.

    Science.gov (United States)

    de la Fuente, Josu; Baruchel, André; Biondi, Andrea; de Bont, Eveline; Dresse, Marie-Françoise; Suttorp, Meinolf; Millot, Frédéric

    2014-10-01

    Chronic myeloid leukaemia in children and young people is a relatively rare form of leukaemia that shows increased incidence with age and some evidence suggests that the molecular basis differs from that in adults. Significant advances in targeted therapy with the development and use in children of tyrosine kinase inhibitors and the ability to monitor and understand the prognostic significance of minimal residual disease by standardized molecular techniques has shifted the management of this condition from bone marrow transplantation as the main therapeutic modality to individualized treatment for each patient based on achieving specific milestones. The physiological changes occurring during childhood, particularly those affecting growth and development and the long-term use of treatment, pose specific challenges in this age group, which we are only beginning to understand.

  18. Incidence of childhood cancer in Preston and South Ribble

    Energy Technology Data Exchange (ETDEWEB)

    Gatrell, A.C.; Whitelegg, J.

    1993-09-01

    Using data from the Manchester Childrens Tumour Register, extending back to 1954, the authors have examined the evidence for clustering of various childhood cancers in Preston and South Ribble, and conclude that incidence in the Penwortham district of Preston is not detectably higher than in other parts of the study areas. Neoplasms studied were leukaemias, lymphomas and those affecting the central and sympathetic nervous system, kidneys, liver and bone and soft tissues. (Author).

  19. Structural studies on leukaemia inhibitory factor

    Energy Technology Data Exchange (ETDEWEB)

    Norton, R.S.; Maurer, T.; Smith, D.K. [Biomolecular Research Institute, Parville (Australia); Nicola, N.A. [Institute of Medical Research, Melbourne (Australia)

    1994-12-01

    Leukaemia Inhibitory Factor (LIF) is a pleiotropic cytokine that acts on a wide range of target cells, including mega-karyocytes, osteoblasts, hepatocytes, adipocytes, neurons, embryonic stem cells, and primordial germ cells. Many of its activities are shared with other cytokines, particularly interleukin-6, oncostatin-M, ciliary neurotrophic factor, and granulocyte colony-stimulating factor (G-CSF). Although secreted in vivo as a glycoprotein, nonglycosylated recombinant protein expressed in E. coli is fully active and has been used in our nuclear magnetic resonance (NMR) studies of the three-dimensional structure and structure-function relationships of LIF. With 180 amino acids and a molecular mass of about 20 kDa, OF is too large for direct structure determination by two-dimensional and three-dimensional {sup 1}HNMR. It is necessary to label the protein with the stable isotopes {sup 15}N and {sup 13}C and employ heteronuclear three-dimensional NMR in order to resolve and interpret the spectral information required for three-dimensional structure determination. This work has been undertaken with both human LIF and a mouse-human chimaera that binds to the human LIF receptor with the same affinity as the human protein and yet expresses in E. coli at much higher levels. Sequence-specific resonance assignments and secondary structure elements for these proteins will be presented and progress towards determination of their three-dimensional structures described.

  20. Further statement on the incidence of childhood cancer in Wales

    International Nuclear Information System (INIS)

    In March 1999 the Welsh Office asked COMARE to examine two unpublished studies. The first by Busby et al of ''Green Audit'' concluded that there was a significant excess of childhood leukaemia in North Wales associated with residential proximity to the coast. The second study, carried out by Steward et al of the Welsh Cancer Intelligence and Surveillance Unit (WCISU), did not support this conclusion. We were asked to advise as to whether we considered that there was a real raised incidence of childhood leukaemia near the coast of North Wales and whether further study was required. To do this we initially organised a comparison of the figures quoted by both the Green Audit and WCISU with the database held by the Childhood Cancer Research Group (CCRG) in Oxford. This group maintains the National Registry of Childhood Tumours (NRCT), data for which are supplied from a variety of sources including cancer registries but also directly from medical cancer specialists as well as from death certificates. As a consequence this provides an independent check on much of the data on childhood cancer held by cancer registries in Great Britain and is clinically validated. After carrying out the independent check on the number of cases of childhood leukaemia in these Welsh counties it was immediately apparent that the data held by Green Audit, on which the analysis by Busby et al was based, were incorrect. These data were received from the Welsh Cancer Registry (WCR) in 1995. A further data set was received from WCR in 1996 but was not used in the analysis by Busby et al. In June 1999 we issued a statement to the Welsh Office. In that statement we noted that Dr Busby and his colleagues appeared to have used erroneous data in their study. On the basis of the Steward et al data, COMARE also stated that we found no evidence to support the contention that there is an increased incidence of childhood leukaemia or other childhood cancers amongst the Welsh population living close to the

  1. Potential for formation of disinfection by-products from storage of chlorinated surface water in the Basalt aquifer near Fallon, Nevada

    Science.gov (United States)

    Fram, Miranda S.; Maurer, Douglas K.; Lico, Michael S.

    2005-01-01

    Increased pumpage from a basalt aquifer near Fallon, Nevada, has caused its water levels to decline and has induced changes in the quality of water pumped from the basalt. The aquifer is the sole source of water for municipal supply to the city of Fallon, the Naval Air Station Fallon, and the Fallon Paiute-Shoshone Tribe. These changes may be mitigated by storage of surface water in the basalt for subsequent use. Because chlorination of the surface water may be required for storage, the U.S. Geological Survey, in cooperation with the Fallon Paiute-Shoshone Tribe, made laboratory tests using laboratory carbon-organic-free water, surface-water, ground-water, and basaltic-rock samples to determine the potential for formation of disinfection by-products. Experiments with water samples only (no rock and no chlorine) indicated no change in dissolved-organic-carbon (DOC) concentrations over a 20-day reaction period; whereas, all experiments using rock, water, and no chlorine indicated an increase in DOC concentrations. The greatest increase in DOC concentrations for all three water samples occurred in experiments with the rock samples from outcrops on Rattlesnake Hill. Experiments with water only and chlorine yielded a total trihalomethane (THM) concentration of 97.4 ?g/L for the ground-water sample and 347 ?g/L for the surface-water sample. Experiments with mixtures of water, rocks, and chlorine indicated that reactions with the rock consumed chlorine and released significant amounts of organic carbon from the rock, increasing the DOC concentration in the water. The organic carbon in the rocks likely is associated with the secondary clay minerals that line vesicles and fractures in the rocks. THM concentrations were greatest, from 335 to 909 ?g/L, for surface water equilibrated with rock samples from Rattlesnake Hill. However, the concentration of chlorine required to produce these high THM concentrations ranged from 18 to 84 mg/L. The results of the experiments suggest

  2. First-line treatment of chronic myeloid leukaemia

    OpenAIRE

    O'Dwyer, Michael

    2010-01-01

    Since the introduction of imatinib just over a decade ago, there has been a dramatic change in the treatment and prognosis of early chronic phase chronic myeloid Leukaemia (CML). This review article focuses on recent advances, culminating in the approval of nilotinib by the US Food and Drug Administration for the treatment of adult patients with newly diagnosed CML in the chronic phase.

  3. T-cell acute lymphoblastic leukaemia : recent molecular biology findings

    NARCIS (Netherlands)

    Kraszewska, Monika D.; Dawidowska, Malgorzata; Szczepanski, Tomasz; Witt, Michal

    2012-01-01

    For many years, T-cell acute lymphoblastic leukaemia (T-ALL) has been considered and treated as a single malignancy, but divergent outcomes in T-ALL patients receiving uniform treatment protocols encouraged intensive research on the molecular biology of this disease. Recent findings in the field dem

  4. Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia

    NARCIS (Netherlands)

    Daniels, J. M. A.; Vonk-Noordegraaf, A.; Janssen, J. J. W. M.; Postmus, P. E.; van Altena, R.

    2009-01-01

    Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB. There are sev

  5. Improved outcome after relapse in children with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Abrahamsson, Jonas; Clausen, Niels; Gustafsson, Göran;

    2007-01-01

    In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were...

  6. Defective monocyte function in Legionnaires' disease complicating hairy cell leukaemia

    DEFF Research Database (Denmark)

    Nielsen, H; Bangsborg, Jette Marie; Rechnitzer, C;

    1986-01-01

    We describe a case of Legionnaires' disease in a 64-year-old man, in which hairy cell leukaemia was diagnosed after the onset of the infection. Immunological studies revealed a complete suppression of blood monocyte chemotactic and oxidative burst activities. We suggest that in hairy cell leukaem...

  7. Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols.

    Science.gov (United States)

    Pession, A; Rondelli, R; Basso, G; Rizzari, C; Testi, A M; Fagioli, F; De Stefano, P; Locatelli, F

    2005-12-01

    Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (P<0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P=0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

  8. Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus

    Directory of Open Access Journals (Sweden)

    Ben-David Yaacov

    2010-01-01

    Full Text Available Abstract Background Acute erythro- and megakaryoblastic leukaemias are associated with very poor prognoses and the mechanism of blastic transformation is insufficiently elucidated. The murine Graffi leukaemia retrovirus induces erythro- and megakaryoblastic leukaemias when inoculated into NFS mice and represents a good model to study these leukaemias. Methods To expand our understanding of genes specific to these leukaemias, we compared gene expression profiles, measured by microarray and RT-PCR, of all leukaemia types induced by this virus. Results The transcriptome level changes, present between the different leukaemias, led to the identification of specific cancerous signatures. We reported numerous genes that may be potential oncogenes, may have a function related to erythropoiesis or megakaryopoiesis or have a poorly elucidated physiological role. The expression pattern of these genes has been further tested by RT-PCR in different samples, in a Friend erythroleukaemic model and in human leukaemic cell lines. We also screened the megakaryoblastic leukaemias for viral integrations and identified genes targeted by these integrations and potentially implicated in the onset of the disease. Conclusions Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time.

  9. Childhood cancer and residential exposure to highways: a nationwide cohort study

    International Nuclear Information System (INIS)

    Children living near highways are exposed to higher concentrations of traffic-related carcinogenic pollutants. Several studies reported an increased risk of childhood cancer associated with traffic exposure, but the published evidence is inconclusive. We investigated whether cancer risk is associated with proximity of residence to highways in a nation-wide cohort study including all children aged <16 years from Swiss national censuses in 1990 and 2000. Cancer incidence was investigated in time to event analyses (1990–2008) using Cox proportional hazards models and incidence density analyses (1985–2008) using Poisson regression. Adjustments were made for socio-economic factors, ionising background radiation and electromagnetic fields. In time to event analysis based on 532 cases the adjusted hazard ratio for leukaemia comparing children living <100 m from a highway with unexposed children (≥500 m) was 1.43 (95 % CI 0.79, 2.61). Results were similar in incidence density analysis including 1367 leukaemia cases (incidence rate ratio (IRR) 1.57; 95 % CI 1.09, 2.25). Associations were similar for acute lymphoblastic leukaemia (IRR 1.64; 95 % CI 1.10, 2.43) and stronger for leukaemia in children aged <5 years (IRR 1.92; 95 % CI 1.22, 3.04). Little evidence of association was found for other tumours. Our study suggests that young children living close to highways are at increased risk of developing leukaemia

  10. Childhood cancer and residential exposure to highways: a nationwide cohort study.

    Science.gov (United States)

    Spycher, Ben D; Feller, Martin; Röösli, Martin; Ammann, Roland A; Diezi, Manuel; Egger, Matthias; Kuehni, Claudia E

    2015-12-01

    Children living near highways are exposed to higher concentrations of traffic-related carcinogenic pollutants. Several studies reported an increased risk of childhood cancer associated with traffic exposure, but the published evidence is inconclusive. We investigated whether cancer risk is associated with proximity of residence to highways in a nation-wide cohort study including all children aged electromagnetic fields. In time to event analysis based on 532 cases the adjusted hazard ratio for leukaemia comparing children living <100 m from a highway with unexposed children (≥500 m) was 1.43 (95 % CI 0.79, 2.61). Results were similar in incidence density analysis including 1367 leukaemia cases (incidence rate ratio (IRR) 1.57; 95 % CI 1.09, 2.25). Associations were similar for acute lymphoblastic leukaemia (IRR 1.64; 95 % CI 1.10, 2.43) and stronger for leukaemia in children aged <5 years (IRR 1.92; 95 % CI 1.22, 3.04). Little evidence of association was found for other tumours. Our study suggests that young children living close to highways are at increased risk of developing leukaemia. PMID:26520639

  11. Childhood cancer and residential radon exposure - results of a population-based case-control study in Lower Saxony (Germany)

    Energy Technology Data Exchange (ETDEWEB)

    Kaletsch, U.; Kaatsch, P.; Meinert, R.; Schuez, J.; Michaelis, J. [Institut fuer Medizinische Statistik und Dokumentation, Johannes-Gutenberg-Universitaet, D-55101 Mainz (Germany); Czarwinski, R. [Bundesamt fuer Strahlenschutz, Fachbereich ST, D-10318 Berlin (Germany)

    1999-09-01

    A population-based case-control study on risk factors for childhood malignancies was used to investigate a previously reported association between elevated indoor radon concentrations and childhood cancer, with special regard to leukaemia. The patients were all children suffering from leukaemia and common solid tumours (nephroblastoma, neuroblastoma, rhabdomyosarcoma, central nervous system (CNS) tumours) diagnosed between July 1988 and June 1993 in Lower Saxony (Germany) and aged less than 15 years. Two population-based control groups were matched by age and gender to the leukaemia patients. Long-term (1 year) radon measurements were performed in those homes where the children had been living for at least 1 year, with particular attention being paid to those rooms where they had stayed most of the time. Due to the sequential study design, radon measurements in these rooms could only be done for 36% (82 leukaemias, 82 solid tumours and 209 controls) of the 1038 families initially contacted. Overall mean indoor radon concentrations (27 Bq m{sup -3}) were low compared with the measured levels in other studies. Using a prespecified cutpoint of 70 Bq m{sup -3}, no association with indoor radon concentrations was seen for the leukaemias (odds ratio (OR): 1.30; 95% confidence interval (95% CI): 0.32-5.33); however, the risk estimates were elevated for the solid tumours (OR: 2.61; 95% CI: 0.96-7.13), mainly based on 6 CNS tumours. We did not find any evidence for an association between indoor radon and childhood leukaemia, which is in line with a recently published American case-control study. There is little support for an association with CNS tumours in the literature. (orig.)

  12. Childhood Stress

    Science.gov (United States)

    ... 5 Things to Know About Zika & Pregnancy Childhood Stress KidsHealth > For Parents > Childhood Stress Print A A ... and feel stress to some degree. Sources of Stress Stress is a function of the demands placed ...

  13. Childhood Obesity

    OpenAIRE

    Wilkinson, Justine; Howard, Simon

    2014-01-01

    Childhood obesity has important consequences for health and wellbeing both during childhood and also in later adult life. The rising prevalence of childhood obesity poses a major public health challenge in both developed and developing countries by increasing the burden of chronic non-communicable diseases. Despite the urgent need for effective preventative strategies, there remains disagreement over its definition due to a lack of evidence on the optimal cut-offs linking childhood BMI to dis...

  14. Childhood Cancer

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Childhood Cancer KidsHealth > For Parents > Childhood Cancer Print A A A Text Size What's ... in children, but can happen. The most common childhood cancers are leukemia , lymphoma , and brain cancer . As ...

  15. A meta-analysis of leukaemia risk from protracted exposure to low-dose gamma radiation

    OpenAIRE

    Daniels, R D; Schubauer-Berigan, M K

    2010-01-01

    Context More than 400 000 workers annually receive a measurable radiation dose and may be at increased risk of radiation-induced leukaemia. It is unclear whether leukaemia risk is elevated with protracted, low-dose exposure. Objective We conducted a meta-analysis examining the relationship between protracted low-dose ionising radiation exposure and leukaemia. Data sources Reviews by the National Academies and United Nations provided a summary of informative studies published before 2005. PubM...

  16. High-flow priapism in acute lymphatic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A. [Institute of Diagnostic and Interventional Radiology, Department of Pediatric Radiology, Friedrich-Schiller-Universitaet Jena, Bachstrasse 18, 07740, Jena (Germany); Kentouche, Karim; Doerfel, Claus; Zintl, Felix [Department of Paediatrics, University of Jena (Germany)

    2004-07-01

    Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

  17. Depleted uranium and radiation - induced lung cancer and leukaemia

    International Nuclear Information System (INIS)

    Reports of leukaemias and other cancers among servicemen who took part in the 1991 Gulf war or in the more recent operations in the Balkans are of continuing interest, as is the possibility, however slight, that depleted uranium (DU) is one of the causative factors. This commentary includes the results of a UK epidemiological study on the mortality of Gulf war veterans and , although not containing information on DU exposure, gives data on overall levels of mortality and therefore carries more weight than anecdotal reports. Also included are brief summaries on radiation-induced lung cancer in uranium workers as well as radiation-induced leukaemia in Japanese atomic bomb survivors and patients ankylosing spondylitis treated using x-rays. This commentary concludes with a critique of Iraqi cancer statistics as well as giving information on environmental contamination in Kosovo and the use of DU ammunition. (author)

  18. Extramedullary Myeloid Cell Tumour Presenting As Leukaemia Cutis

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2002-01-01

    Full Text Available We herewith report a case of extramedullary myeloid cell tumour presenting as leukaemia cutis for its rarity. It occurred in a 50 year old male patient who presented to us with a 40 days history of painless raised solid skin swellings over the trunk. Histopathological examination of the skin biopsy and bone marrow biopsy showed features suggestive of non-Hodgkin’s lymphoma. Immunophenotyping on skin biopsy specimens and bone marrow biopsy found tumour cells expressing CD43 and Tdt but were negative for CD3 and CD20. These features were consistent with extramedullary myeloid cell tumour involving skin and subcutis (cutaneous manifestation of acute myeloid leukaemia.

  19. Longitudinal assessment of nutritional status in children treated for acute lymphoblastic leukaemia in Cuba.

    Science.gov (United States)

    González, A; Cortina, L; González, P; González, C; García, T; de Svarch, E G

    2004-05-01

    Malnutrition has a deleterious effect on the results of therapy for malignant diseases in childhood. The impact of radiotherapy on growth is well known but the impact of cytotoxic drugs on nutritional status is more controversial. The purpose of this study was to determine the nutritional status of a cohort of children treated for acute lymphoblastic leukaemia (ALL) in Cuba. The study involved 49 children admitted to a single center and treated with a Berlin-Frankfurt-Munster-based protocol. Nutritional assessment included measurements of height, weight, body mass index and skin-fold thickness, made at diagnosis, after the intensive phase of treatment and at the end of therapy. Z-scores were used for height and comparison of percentiles for the rest of the variables. All the patients were above the third percentile in all the measurements. There were no statistically significant differences between the results at diagnosis, after intensive therapy and at the end of treatment. Although the sample was small, there was no demonstrable effect of chemotherapy on nutritional status in this Cuban paediatric population, in contrast to that reported in children with ALL in other developing countries.

  20. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  1. The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia.

    Science.gov (United States)

    Stumpel, Dominique J P M; Schneider, Pauline; Pieters, Rob; Stam, Ronald W

    2015-09-01

    MLL-rearranged acute lymphoblastic leukaemia (ALL) in infants is the most difficult-to-treat type of childhood ALL, displaying a chemotherapy-resistant phenotype, and unique histone modifications, gene expression signatures and DNA methylation patterns. MLL-rearranged infant ALL responds remarkably well to nucleoside analogue drugs in vitro, such as cytarabine and cladribine, and to the demethylating agents decitabine and zebularine as measured by cytotoxicity assays. These observations led to the inclusion of cytarabine into the treatment regimens currently used for infants with ALL. However, survival chances for infants with MLL-rearranged ALL do still not exceed 30-40%. Here we explored the in vitro potential of the novel nucleoside analogue clofarabine for MLL-rearranged infant ALL. Therefore we used both cell line models as well as primary patient cells. Compared with other nucleoside analogues, clofarabine effectively targeted primary MLL-rearranged infant ALL cells at the lowest concentrations, with median LC50 values of ∼25 nM. Interestingly, clofarabine displayed synergistic cytotoxic effects in combination with cytarabine. Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Demethylation of the FHIT promoter region was accompanied by subtle re-expression of this gene both at the mRNA and protein level. We conclude that clofarabine is an interesting candidate for further studies in MLL-rearranged ALL in infants. PMID:26188848

  2. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma.

    Science.gov (United States)

    Nysom, K; Holm, K; Hesse, B; Ulrik, C S; Jacobsen, N; Bisgaard, H; Hertz, H

    1996-05-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation.

  3. Risk of leukaemia and other cancers in Seascale

    Energy Technology Data Exchange (ETDEWEB)

    Fry, F. [National Radiological Protection Board, Chilton (United Kingdom)

    1995-10-01

    NRPB has recently published revised estimates of the radiation dose and the risk of radiation-induced leukaemias and other cancers in children and young persons living in Seascale, Cumbria. The work was undertaken at the request of the Committee on the Medical Aspects of Radiation in the Environmental (COMARE) and close liaison was maintained with COMARE and its working groups during the study. This short article outlines the approach adopted and summarises the results. (Author).

  4. Atypical Chronic Myeloid Leukaemia with Trisomy 13: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Guo-yu Hu; Chao-hui Yuan; Kui Tan; Zhen-zhen Chen

    2011-01-01

    ATYPICAL chronic myeloid leukaemia (aCML),which shows both myeloproliferative and myeIodysplastic features,is a type of myeloproliferative/myelodysplastic disease as defined by the World Health Organisation (WHO) classification of the myeloid neoplasms.1 Because of the presence of neutrophilic leukocytosis,aCML may resemble chronic myeIogenous leukemia (CML).However,in contrast with CML,aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.

  5. Acute Myeloid Leukaemia: Optimal Management and Recent Developments

    OpenAIRE

    Villela, Luis; Bolaños-Meade, Javier

    2011-01-01

    The current treatment of patients with acute myeloid leukaemia yields poor results, with expected cure rates in the order of 30–40% depending on the biological characteristics of the leukaemic clone. Therefore, new agents and schemas are intensively studied in order to improve patients’ outcomes. This review summarizes some of these new paradigms, including new questions such as which anthracycline is most effective and at what dose. High doses of daunorubicin have shown better responses in y...

  6. New genetics and diagnosis of childhood B-cell precursor acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Christine Harrison

    2011-06-01

    Full Text Available Over the last 50 years, while significant advances have been made in the successful treatment of childhood leukaemia, similar progress has been made in understanding the genetics of the disease. In childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL, the incidences of individual chromosomal abnormalities are well established and cytogenetics provides a reliable tool for risk stratification for treatment. In spite of this role, a number of patients will relapse. Increasing numbers of additional genetic changes, including deletions and mutations, are being discovered. Their associations with established cytogenetic subgroups and with each other remain unclear. Whether they have a link to outcome is the most important factor in terms of refinement of risk factors in relation to clinical trials. For a number of newly identified abnormalities, appropriately modified therapy has significantly improved outcome. Alternatively, some of these aberrations are providing novel molecular markers for targeted therapy.

  7. Feline leukaemia virus and its clinical effects in cats.

    Science.gov (United States)

    Mackey, L

    1975-01-01

    Feline leukemia virus (FeLV) infection is common among cats where contact is high. The virus can be transmitted readily between cats. It causes a variety of haemopoietic and lymphoid neoplasms; the most common types are alimentary, multicentric and thymic lymphosarcoma and lymphatic leukaemia. The virus is involved in the aetiology of certain other diseases including anaemia, glomerulonephritis and an immunosuppressive syndrome which predisposes cats to intercurrent infections. Many infected cats mount an immune response and do not suffer from any of these. The immune status is shown by serum antibody levels to feline leukaemia virus associated cell membrane antigens. Cats with a titre of 32 or more are most unlikely to suffer any ill effects and may eliminate the virus infection. The outcome of infection in an individual cat depends on the immunological competence of the cat, the dose of virus received and its ability to induce immunosuppression. FeLV infection can be detected by examination of tissues by electron microscopy, and by culture of virus from plasma and other tissues. In the United States, a method is now in use for the detection of leukaemia virus antigen in peripheral blood leukocytes; this is carried out on ordinary blood films. Successful prototype vaccines have been developed against FeLV. This paper describes the natural history of the virus, the diseases in which it is implicated and discusses recently developed diagnostic methods. PMID:163515

  8. 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.

  9. Identification of novel Notch target genes in T cell leukaemia

    Directory of Open Access Journals (Sweden)

    Warrander Fiona

    2009-06-01

    Full Text Available Abstract Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE, and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1. Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

  10. CD19-Chimeric Antigen Receptor T Cells for Treatment of Chronic Lymphocytic Leukaemia and Acute Lymphoblastic Leukaemia

    DEFF Research Database (Denmark)

    Lorentzen, C L; thor Straten, Per

    2015-01-01

    Adoptive cell therapy (ACT) for cancer represents a promising new treatment modality. ACT based on the administration of cytotoxic T cells genetically engineered to express a chimeric antigen receptor (CAR) recognizing CD19 expressed by B cell malignancies has been shown to induce complete lasting...... responses in patients with chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL). So far, eleven clinical trials including 99 CLL and ALL patients treated with CAR T cells targeting CD19 have been published, and the results from these trials are promising with impressive clinical...... responses in heavily pretreated patients. Thus, CAR T cell therapy has induced complete responses in both CLL and ALL, and surprisingly, current results indicate that patients with ALL are more prone to respond than are CLL patients. Importantly, the majority of CAR cell studies have observed severe therapy...

  11. The Role of HDACs Inhibitors in Childhood and Adolescence Acute Leukemias

    OpenAIRE

    Riccardo Masetti; Salvatore Serravalle; Carlotta Biagi; Andrea Pession

    2011-01-01

    Acute leukemia is the most common type of childhood and adolescence cancer, characterized by clonal proliferation of variably differentiated myeloid or lymphoid precursors. Recent insights into the molecular pathogenesis of leukemia have shown that epigenetic modifications, such as deacetylation of histones and DNA methylation, play crucial roles in leukemogenesis, by transcriptional silencing of critical genes. Histone deacetylases (HDACs) are potential targets in the treatment of leukaemia,...

  12. Seasonal variations in the diagnosis of childhood cancer in the United States

    OpenAIRE

    Ross, J A; Severson, R K; Swensen, A R; Pollock, B H; Gurney, J G; Robison, L.L.

    1999-01-01

    Seasonal trends in month of diagnosis have been reported for childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). This seasonal variation has been suggested to represent an underlying viral aetiology for these malignancies. Some studies have shown the highest frequency of diagnoses in the summer months, although this has been inconsistent. Data from the Children's Cancer Group and the Pediatric Oncology Group were analysed for seasonal incidence patterns. A total of...

  13. Childhood cancer and paternal employment in agriculture: the role of pesticides.

    OpenAIRE

    Fear, N T; E. ROMAN; G. Reeves; Pannett, B

    1998-01-01

    Previous studies have suggested that the offspring of men potentially exposed to pesticides at work may be at increased risk of kidney cancer (Wilms' tumour), brain tumours, Ewing's bone sarcoma and acute leukaemia. This paper examines the association between potential occupational exposure of fathers to pesticides and offspring's death from cancer in a large national database. Records for 167703 childhood deaths occurring during 1959-63, 1970-78 and 1979-90 in England and Wales have been ana...

  14. Committee on Medical Aspects of Radiation in the Environment (COMARE) 4. report. The incidence of cancer and leukaemia in young people in the vicinity of the Sellafield site, West Cumbria: Further studies and an update of the situation since the publication of the report of the Black Advisory Group in 1984

    International Nuclear Information System (INIS)

    The Fourth Report of the Committee on Medical Aspects of Radiation in the Environment (COMARE) updates the information on the incidence of cancer and leukaemia in young people in the vicinity of the Sellafield site since the publication of the Black Advisory Group report in 1984. Data are reviewed on radiation exposure and the risk of radiation-induced leukaemia and cancer in young people living in Seascale; possible effects of paternal preconception irradiation in cancer; exposure to chemicals used at and discharged from the Sellafield site and the risk to the general population and offspring of site workers; and the infectious aetiology of childhood cancer. The history of the Royal Ordnance Factories sited at Sellafield and Drigg in the 1940s and a historical review of childhood cancer in Seascale is also given. (UK)

  15. CBL mutations do not frequently occur in paediatric acute myeloid leukaemia

    NARCIS (Netherlands)

    Coenen, Eva A.; Driessen, Emma M. C.; Zwaan, C. Michel; Stary, Jan; Baruchel, Andre; de Haas, Valerie; de Bont, Eveline S. J. M.; Reinhardt, Dirk; Kaspers, Gertjan J. L.; Arentsen-Peters, Susan T. C. J. M.; Meyer, Claus; Marschalek, Rolf; Pieters, Rob; Stam, Ronald W.; van den Heuvel-Eibrink, Marry M.

    2012-01-01

    RAS-pathway mutations, causing a proliferative advantage, occur in acute myeloid leukaemia (AML) and MLL-rearranged leukaemia. Recently, mutations in the Casitas B lineage lymphoma (CBL) gene were reported to be involved in RAS-pathway activation in various myeloid malignancies, but their role in pa

  16. Acute leukaemia after exposure to a weed killer, 2-methyl-4-chlorphenoxyacetic acid.

    Science.gov (United States)

    Timonen, T T; Palva, I P

    1980-01-01

    Acute leukaemia is known to develop in many cases of benzene-induced pancytopenia [1]. This is a report of the development of acute leukaemia in a patient who had apparently recovered from pancytopenia after chronic exposure to a weed killer, 2-methyl-4-chlorphenoxyacetic acid. PMID:6769284

  17. Childhood Obesity

    OpenAIRE

    Aydın, Ahmet; Koca, Fahrettin; Fıçıcıoğlu, Can; Çam, Halit; Mıkla, Şerare

    1995-01-01

    Management of childhood obesity and its early and late complications are among the most difficult problems confronted by pediatricians and practitioners The purpose of this review is to provide information for the evaluation and treatment of childhood obesity Key nbsp;words: nbsp;Child Obesity Etiology Management Complications

  18. Quantitative variation of superoxide dismutase levels in leukaemias

    Directory of Open Access Journals (Sweden)

    Poongothai A

    2004-01-01

    Full Text Available Superoxde dismutase is dimeric antioxidant enzyme responsible for quenching of superoxide radicals which are released during the chemical reactions of the various metabolic pathways .The enzyme levels of SOD are altered to a considerable extent in various diseased states exhibiting either elevation or depletion in their enzymatic activity.As this phenomenon was found to be more evident in leukaemias, we have estimated the Cu-Zn SOD levels in the red cells of the leukaemic patients in order to evaluate the efficiency of anti oxidant system and its relation to leukaemiogenesis. The overall mean SOD levels in the leukaemic patients (AML, ALL and CML were significantly low (124.97±6.46 as compared to that of the normal controls (287.08±6.79. In respect to the age, the mean SOD levels were found to be elevated indicating the extent of the free radicals might have stimulated the production of the antioxidants.In response to chemotherapy, the mean SOD levels were observed to be elevated but not the extent of the normal levels among the treated groups in AML(127.40±8.67 and CML (174.73±53.59 types of leukaemias as compared to that of the untreated groups. In general the stage of leukaemia did not cause any variation in the SOD levels. However, the L2 in ALL (107.49±4.88, blast crisis in CML (154.00±19.86 showed reduced levels of SOD.

  19. Radiation-associated chronic myelogenous leukaemia in younger people

    International Nuclear Information System (INIS)

    Chronic myelogenous leukaemia (CML) is known to be induced by exposure to ionizing radiation, as is acute leukaemia. However, CML has been recorded only rarely as a complication of radiation exposure early in life. During the period from 1973 to 1976, 75 patients with CML were admitted to Roswell Park Memorial Institute (RPMI). In addition, 64 patients admitted to RPMI previously were also available for study in 1973. Among 79 patients who were born after 1925, information regarding radiation exposure was obtained in 89%; 49 were interviewed and 21 responded to a mailed questionnaire. Consultation with parents was achieved in 52 of the 70 responding cases (74%). Replies were obtained from 15 of the 18 patients below the age of 25, and were confirmed by parents or siblings in all instances. Replies to the mailed questionnaire were obtained from 45 age- and sex-matched controls. In addition to two patients already known to have radiation exposure for treatment of malignant neoplasms, these inquiries yielded a total of nine patients with histories of radiation exposure for benign conditions. Three had therapeutic irradiation, two for thymic enlargement and one for eczema. Three had exposure in utero by pelvimetry. Two had diagnostic exposure during the perinatal period and one had occupational exposure as a nurse. Four of these patients were below the age of 25. All nine patients had the Ph' chromosome. The course of CML in these patients was not different from that of other patients with Ph' chromosome-positive CML without a history of radiation exposure. A history of radiation exposure was elicited in one-fourth of the younger patients (<25) in this study, compared with one of 45 age- and sex-matched controls without leukaemia (p<0.02)

  20. Hypoxia and hypoxia-inducible factors in leukaemias

    Directory of Open Access Journals (Sweden)

    Margaux eDeynoux

    2016-02-01

    Full Text Available Despite huge improvements in the treatment of leukaemia, the percentage of patients suffering relapse still remains significant. Relapse most often results from a small number of leukaemic stem cells (LSCs within the bone marrow, which are able to self-renew and therefore re-establish the full tumour. The marrow microenvironment contributes considerably in supporting the protection and development of leukaemic cells. LSCs share specific niches with normal haematopoietic stem cells with the niche itself being composed of a variety of cell types including mesenchymal stem/stromal cells, bone cells, immune cells, neuronal cells and vascular cells. A hallmark of the haematopoietic niche is low oxygen partial pressure, indeed this hypoxia is necessary for the long-term maintenance of HSCs. Hypoxia is a strong signal, principally maintained by members of the hypoxia-inducible factor family. In solid tumours, it has been well-established that hypoxia triggers intrinsic metabolic changes and microenvironmental modifications, such as the stimulation of angiogenesis, through activation of HIFs. As leukaemia is not considered a solid tumour, the role of oxygen in the disease was presumed to be inconsequential and remained long overlooked. This view has now been revised since hypoxia has been shown to influence leukaemic cell proliferation, differentiation and resistance to chemotherapy. However, the role of HIF proteins remains controversial with HIFs being considered as either oncogenes or tumour suppressor genes, depending on the study and model. The purpose of this review is to highlight our knowledge of hypoxia and HIFs in leukaemic development and therapeutic resistance, and to discuss the recent hypoxia-based strategies proposed to eradicate leukaemias.

  1. Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Waal, R.I.F. van der; Waal, I. van der [Univ. Hospital Vrije Univ., Dept. of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam (Netherlands); Veerman, A.J.P. [Univ. Hospital Vrije Univ., Dept. of Paediatric Oncology, Amsterdam (Netherlands); Snow, G.B. [Univ. Hospital Vrije Univ., Dept. of Otorhinolaryngology, Amsterdam (Netherlands)

    1997-02-01

    With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs.

  2. [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...

  3. Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs

  4. [Characteristic of the yeast isolated from patients with leukaemia].

    Science.gov (United States)

    Fedorovskaia, E A; Rybal'skaia, A P; Skachkova, N K; Mel'nik, E A; Nemirovskaia, L N; Nagornaia, S S; Babich, T V; Polishchuk, L V

    2008-01-01

    It has been shown that biotopes of upper respiratory system and intestine were contaminated with yeast in 44.6% of patients with leukaemia (of 112 examined ones). Their quantity exceeds the boundary value for practically healthy people and is > or = 10(2) KOE/ml in the nasal activity and fauces and leucemia the mycotic complications are mainly caused by anamorphous yeast of ascomycetic affinity. Candida albicans, as well as C. glabrata, C. rugosa and Candida sp. play the leading role. The Candida genus species are mainly sensitive to amphotericine B, clotrisamol and nistatin.

  5. The Effects of Herbs and Fruits on Leukaemia

    Directory of Open Access Journals (Sweden)

    Tayebeh Azam Saedi

    2014-01-01

    Full Text Available In developing countries, herbal therapy is the first and basis form of treatment for most types of diseases. About 75–80% of the world’s population prefers herbal therapy as a major treatment due to its better adequacy and satisfactoriness, which enhance human body’s symmetry with minimal side effects. Fruits and plants have been presented from the past as promising tools in becoming a natural anticancer agents. Many of these plant extracts are currently used in cancer therapy and prevention. This review paper will particularly explore and emphasize on herbs and fruits used in the treatment of the leukaemia.

  6. Expression of partial tandem duplication of mixed lineage leukaemia in patients with acute leukaemia and their relatives

    Institute of Scientific and Technical Information of China (English)

    He Yi; Wang Dongning; Li Xudong; Hu Yuan; Wang Wenwen; Huang Renwei

    2014-01-01

    Background Partial tandem duplication of mixed lineage leukaemia (MLL-PTD) is detected both in patients with acute leukemia and in healthy people.However,MLL-PTD in relatives of patients with MLL-PTD has not been reported.The objective of this study was to investigate the expression of MLL-PTD in patients with acute leukemia and in their relatives.Methods The bone marrow or peripheral blood was collected from patients with acute leukaemia and their relatives.Nested reverse transcription-polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression of the MLL-PTD fused gene,and further confirm in genomic DNA level.Results Analysing MLL-PTD in case 1,the patient's older brother and his younger brother were positive,while his mother and his son were negative.The exon type in case 1 was e9/3 fusion,but in his older brother,it was e9/3 and e11/3 fusion,and in his younger brother,it was e9/3,e10/3,and e11/3 fusion.MLL-PTD in case 2 was negative,but in the patient's older sister was positive,and the exon type was e9/3,e10/3,and e11/3.Conclusions The expression of MLL-PTD was present in cases with acute leukaemia with a single expression type.However,various expression types were detected in their healthy relatives.MLL-PTD can couple with other chromosome aberrations,and its impact on disease prognosis remains to be studied further.

  7. Adult leukaemia: what is the role of currently known risk factors?

    Energy Technology Data Exchange (ETDEWEB)

    Zeeb, H. [Deutsches Krebsforschungszentrum, Abt. Epidemiologie, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Blettner, M. [International Agency for Research on Cancer (IARC), Unit of Carcinogen Identification and Evaluation, 150 Cours Albert Thomas, F-69372 Lyon (France)

    1998-02-01

    Leukaemias are a heterogeneous group of tumours including acute and chronic forms. Considerable efforts have been made to identify risk factors for these diseases, but only a minority of leukaemia cases can currently be attributed to identified or hypothesized factors. This review highlights recent epidemiological literature concerning adult leukaemia, discussing in detail the hereditary, environmental and medical risks. Chromosomal syndromes and genetically based diseases carry a high risk of leukaemia, but rarely occur in the population. Environmental and occupational exposures to chemicals including pesticides have been widely studied, although the results are not consistent, with the exception of benzene. Smoking seems to be a weak causal risk factor. The risk of ionizing radiation has further been quantified in recent studies, although the effects of low doses have not yet been clarified. The results for non-ionizing radiation continue to be inconsistent, but a large effect of electromagnetic fields on the risk of leukaemia appears to be unlikely. Medically applied radio- and chemotherapy are clearly associated with subsequent leukaemia development, and there are links between leukaemia and viral infections. Future research should emphasize the shortcomings in exposure assessment that pervade many studies, and interactions between different risk factors need to be taken into consideration. (orig.) With 1 fig., 5 tabs., 114 refs.

  8. Traffic-related air pollution and risk for leukaemia of an adult population.

    Science.gov (United States)

    Raaschou-Nielsen, Ole; Ketzel, Matthias; Harbo Poulsen, Aslak; Sørensen, Mette

    2016-03-01

    Air pollution causes lung cancer, but associations with other cancers have not been established. We investigated whether long-term exposure to traffic-related air pollution is associated with the risk of the general population for leukaemia. We identified 1,967 people in whom leukaemia was diagnosed in 1992-2010 from a nation-wide cancer registry and selected 3,381 control people at random, matched on sex and year of birth, from the entire Danish population. Residential addresses since 1971 were traced in a population registry, and outdoor concentrations of NOx and NO2 , as indicators of traffic-related air pollution, were calculated at each address in a dispersion model. We used conditional logistic regression to estimate the risk for leukaemia after adjustment for income, educational level, cohabitation status and co-morbidity. In linear analyses, we found odds ratios for acute myeloid leukaemia of 1.20 (95% confidence interval: 1.04-1.38) per 20 µg/m(3) increase in NOx and 1.31 (1.02-1.68) per 10 µg/m(3) increase in NO2 , calculated as time-weighted average exposure at all addresses since 1971. We found no association with chronic myeloid or lymphocytic leukaemia. This study indicates an association between long-term exposure to traffic-related air pollution and acute myeloid leukaemia in the general population, but not for other subtypes of leukaemia. PMID:26415047

  9. Childhood Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  10. Using multistage models to describe radiation-induced leukaemia

    International Nuclear Information System (INIS)

    The Armitage-Doll model of carcinogenesis is fitted to data on leukaemia mortality among the Japanese atomic bomb survivors with the DS86 dosimetry and on leukaemia incidence in the International Radiation Study of Cervical Cancer patients. Two different forms of model are fitted: the first postulates up to two radiation-affected stages and the second additionally allows for the presence at birth of a non-trivial population of cells which have already accumulated the first of the mutations leading to malignancy. Among models of the first form, a model with two adjacent radiation-affected stages appears to fit the data better than other models of the first form, including both models with two affected stages in any order and models with only one affected stage. The best fitting model predicts a linear-quadratic dose-response and reductions of relative risk with increasing time after exposure and age at exposure, in agreement with what has previously been observed in the Japanese and cervical cancer data. However, on the whole it does not provide an adequate fit to either dataset. The second form of model appears to provide a rather better fit, but the optimal models have biologically implausible parameters (the number of initiated cells at birth is negative) so that this model must also be regarded as providing an unsatisfactory description of the data. (author)

  11. MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia

    Directory of Open Access Journals (Sweden)

    Imilia Ismail

    2014-01-01

    Full Text Available Acute promyelocytic leukaemia (APL is an M3 subtype of acute myeloid leukaemia (AML. This classification is based on the morphology of promyelocytic cell. The clinical characteristics of APL can be recognized by haemorrhagic episodes, a differentiation block at the promyelocytic stage, and sensitivity to the differentiation response to all-trans-retinoic acid (ATRA. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the production of PML/RARα fusion protein. Recent studies reported that microRNAs (miRNAs have also been proposed to contribute to the pathogenesis of APL. miRNAs have been associated with the pathogenesis of cancer and their involvement as oncogenic and tumour suppressor activities have been identified. They are involved in various biological processes including the cell proliferation, differentiation, growth and development, metabolism, apoptosis, and haematopoiesis. The new discovery of miRNAs as possible therapeutic markers will provide new insight for the diagnosis and therapeutic entries for the treatment of APL. This review highlights the potential of miRNAs as biomarkers in APL.

  12. Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

    Science.gov (United States)

    Cazzaniga, Giovanni; Lanciotti, Marina; Rossi, Vincenzo; Di Martino, Daniela; Aricò, Maurizio; Valsecchi, Maria Grazia; Basso, Giuseppe; Masera, Giuseppe; Micalizzi, Concetta; Biondi, Andrea

    2002-11-01

    Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

  13. The incidence of and mortality from leukaemias in the UK: a general population-based study

    Directory of Open Access Journals (Sweden)

    McKeever Tricia

    2009-07-01

    Full Text Available Abstract Background The acute and chronic leukaemias constitute about 2.5% of all newly diagnosed malignancies and kill over 4000 people/year in the UK, yet there is little accurate up-to-date data on how the incidence of and mortality from leukaemias vary with socio-economic status in the UK. We aimed to quantify the incidence of and mortality from leukaemias in the UK and their variation with gender, age, year of diagnosis as well as socio-economic status. Methods All incident cases of leukaemia were identified in 'The Health Improvement Network' (THIN General Practice dataset. Crude incidence rates and incidence rate ratios (using Poisson Regression stratified by age, gender, year of diagnosis and socio-economic status were calculated. Median survival and hazard ratios for risk of death (using Cox regression were then calculated, and stratified in a similar manner. Results A total of 4162 cases of leukaemia were identified, 2314 (56% of whom were male. The overall incidence of leukaemia was 11.25 per 100 000 person-years. The age and gender distributions of ALL, AML, CLL and CML were similar to UK cancer registry data. The incidence of leukaemias was independent of socio-economic class. Median survival from leukaemia was 6.58 years and mortality increased with increasing age at diagnosis. The prognosis in AML was dismal and worsened with increasing socio-economic deprivation. For other leukaemias mortality was independent of socio-economic status. Conclusion This is the first general population study to describe the incidence of and mortality from leukaemias in the UK by socio-economic status. Similar mortality across socio-economic gradients in the leukaemias studied suggests equal access to and uptake of services. The exception to this was in AML, where poorer survival in AML patients from lower socio-economic classes may represent a class bias in treatment offered and/or greater co-morbidity in these patients, and warrants further

  14. Intellectual Abilities Among Survivors of Childhood Leukaemia as a Function of CNS Irradiation

    Science.gov (United States)

    Eiser, Christine

    1978-01-01

    Available from: British Medical Journal, 1172 Commonwealth Avenue, Boston, Massachusetts 02134. In order to determine whether Central Nervous System irradiation effects intellectual abilities, 28 children in remission at least 2 years after completing chemotherapy for acute lymphoblastic leukemia were assessed on standardized psychological tests…

  15. Host genome variations and risk of infections during induction treatment for childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Lund, Bendik; Wesolowska-Andersen, Agata; Lausen, Birgitte;

    2014-01-01

    .01). Classification and regression tree analysis demonstrated rs11033797 (OR51F1), rs2835265 (CBR1), rs28627172 (POLDIP3) and rs1129844 (CCL11) to be predictive of outcome. Among 61 patients for whom read-outs were available for all four SNPs, 40 of 41 patients with the worst SNP profile experienced at least one...... infectious event compared with five of the remaining 20 patients (Hazard ratio 9.0, 95% CI 3.4–23.5, which was unchanged after adjustments for neutrophil counts). Pathway analysis identified variations in ‘G-protein-coupled receptor (GPCR) downstream signalling’, ‘Bile acid and bile salt metabolism...

  16. Childhood leukaemia, non-Hodgkin lymphoma and Hodgkin diseases in Eastern Romania between 1980 and 1994

    International Nuclear Information System (INIS)

    The radiation exposure of children during the first 3 years following the Chernobyl accident (May 1986 - April 1989) was expressed in terms of effective dose, the dosimetric quantity recommended by I.C.R.P. in Publication 60. The effective doses resulted from internal radiation by ingestion of contaminated food were estimated from the radioactive content of foodstuffs (134 - Cs, 137 - Cs determined by high-resolution gammaspectrometric techniques and 90 - Sr by a sensitive radiochemical methods). The average annual food consumption and the corresponding I.C.R.P. dose factors. 15 refs, 3 figs, 8 tabs

  17. Birth weight in offspring and leukaemia risk in parents-A nation-wide register-based cohort study from Denmark

    DEFF Research Database (Denmark)

    Marklund, Maria; Rostgaard, Klaus; Hjalgrim, Lisa;

    2013-01-01

    Spurred by previous observations we assessed the relationship between offspring birth weight and parental leukaemia risk in a register-based investigation including 2.4 million parents of 2 million Danish children. Regardless of analytical approach, offspring birth weight was not associated with...... parental risk of leukaemia overall or of leukaemia subtypes except for a twofold increased acute lymphatic leukaemia risk in fathers of high birth weight offspring and an increasing paternal risk of chronic myeloid leukaemia with increasing offspring birth weight. These may both be chance findings. Our...... investigation indicates that offspring birth weight is not strongly associated with parental leukaemia risk....

  18. Oral methotrexate is as effective as intramuscular in maintenance therapy of acute lymphoblastic leukaemia.

    OpenAIRE

    Chessells, J M; Leiper, A D; Tiedemann, K.; Hardisty, R. M.; Richards, S.

    1987-01-01

    It has been postulated that variations in methotrexate absorption may influence the outcome of treatment in lymphoblastic leukaemia. One hundred and forty four children with acute lymphoblastic leukaemia not of the T cell type were randomised to receive continuing treatment with daily 6-mercaptopurine, vincristine, and prednisolone six weekly and methotrexate once weekly, either as a single oral dose or an intramuscular injection. Analysis of results with a minimum follow up of three and a ha...

  19. [Necrotizing tonsillitis and renal vein thrombosis due to acute myeloid leukaemia].

    Science.gov (United States)

    Akram, Javed; Josefsson, Pernilla; Rømeling, Frans

    2012-09-01

    A 37-year-old woman was admitted to hospital with severe tonsillitis with unilateral necrotizing tonsillitis. She suddenly got fever, malaise, difficulties swallowing, pain in the throat and deterioration despite four days of penicillin treatment. During hospitalisation, she experienced abdominal pain, and blood tests showed pancytopenia. She was transferred to a haematological department, where a bone marrow biopsy showed acute myeloid leukaemia. Subsequently, an abdominal computed tomography with intravenous contrast revealed bilateral renal vein thrombosis, probably because of coagulopathy due to leukaemia.

  20. Childhood obesity

    DEFF Research Database (Denmark)

    Heitmann, Berit L; Koplan, Jeffrey; Lissner, Lauren

    2009-01-01

    Despite progress toward assuring the health of today's young population, the 21(st) century began with an epidemic of childhood obesity. There is general agreement that the situation must be addressed by means of primary prevention, but relatively little is known about how to intervene effectively....... The evidence behind the assumption that childhood obesity can be prevented was discussed critically in this roundtable symposium. Overall, there was general agreement that action is needed and that the worldwide epidemic itself is sufficient evidence for action. As the poet, writer, and scholar Wittner Bynner...

  1. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

    Science.gov (United States)

    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  2. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation.

    Science.gov (United States)

    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  3. Leukaemia inhibitory factor--an exercise-induced myokine

    DEFF Research Database (Denmark)

    Broholm, Christa; Pedersen, Bente Klarlund

    2010-01-01

    During and following exercise skeletal muscle synthesises and releases a number of myokines that exert their effects either systemically or locally within the muscle. Several of these myokines influence metabolism, regeneration and/or hypertrophy and are therefore considered to be important...... to oscillations in intracellular Ca2+ concentrations. However, circulating levels of LIF are not increased with exercise suggesting that LIF exerts its effect locally. LIF stimulates muscle satellite cell proliferation and is involved in muscle hypertrophy and regeneration. Thus, LIF may be produced by skeletal...... contributing factors in muscle homeostasis and muscle adaptation to exercise training. Leukaemia inhibitory factor (LIF) is produced and released from muscle cells in vitro and from intact skeletal muscle in vivo. During exercise, skeletal muscle potently up-regulates LIF mRNA expression, likely due...

  4. Orbital mass secondary to infantile acute lymphoblastic leukaemia.

    Science.gov (United States)

    Hossain, Ibtesham Tausif; Moosajee, Mariya; Abou-Rayyah, Yassir; Pavasovic, Vesna

    2016-01-01

    An 8-month-old Asian infant girl was referred with a 1-week history of left periorbital swelling on a background of a narrowed left palpebral aperture over the preceding 8 weeks. There was no history of chronic illness, fever or other systemic features. Examination revealed a tender and fluctuant medial canthal swelling with associated periorbital haematoma. There were no other ophthalmic findings and neurological examination was normal. A MRI scan of the brain and orbit demonstrated abnormal soft tissue with features of an aggressive tumour in the left orbital region with no globe invasion. Peripheral blood smear revealed blast cells, confirmed by bone marrow aspirate. A diagnosis of infant acute lymphoblastic leukaemia was made. The patient was started on risk-stratified chemotherapy according to the Interfant-06 Protocol The periorbital swelling resolved by day eight following a course of prednisolone, the patient continues on chemotherapy and is currently in molecular remission. PMID:27143162

  5. Leukaemia and non-Hodgkin lymphoma risk among Chernobyl liquidators

    International Nuclear Information System (INIS)

    Full text: Chernobyl liquidators were workers involved in the clean-up of contaminated areas around the Chernobyl power plant following the accident on 26 April 1986. These workers form a potentially important population for evaluation of the effects of protracted low doses of ionizing radiation. A collaborative case-control study of leukaemia and non-Hodgkin lymphoma (NHL) was set-up, nested within cohorts of Belarus, Russian and Baltic countries liquidators. The objective was to evaluate the radiation-induced risk of these diseases in this population and to study the effect of exposure protraction and radiation type on the risk of radiogenic cancer in the low to medium (0-500 mSv) radiation dose range. The study population consisted of approximately 66,000 Belarus, 65,000 Russian and 15,000 Baltic countries liquidators who took part in the clean-up activities between 26 April 1986 and 31 December 1987. In Belarus and Russia, liquidators are followed through the Chernobyl Registries and must undergo regular health check-ups, while in the Baltic countries their migration, vital and cancer status are assessed through population, death and cancer registries. The case ascertainment period ranged from 1990 to 2000 with minor differences among the countries. Information on study subjects was obtained through a face-to-face interview with the study subject and/or a proxy (a relative or a colleague), using a standardized questionnaire on demographic factors, time, place and conditions of work as a liquidator and on potential risk and confounding factors for leukaemia. A method of analytical dose reconstruction, entitled RADRUE (Realistic Analytical Dose Reconstruction with Uncertainty Estimation), was developed within the study, validated and applied to estimate individual dose to the bone marrow and related uncertainties for each subject. 117 cases (69 leukaemia, 34 NHL and 14 other malignancies of lymphoid and haematopoietic tissue) and 481 matched controls were

  6. Leukaemia inhibitory factor--an exercise-induced myokine

    DEFF Research Database (Denmark)

    Broholm, Christa; Pedersen, Bente Klarlund

    2010-01-01

    During and following exercise skeletal muscle synthesises and releases a number of myokines that exert their effects either systemically or locally within the muscle. Several of these myokines influence metabolism, regeneration and/or hypertrophy and are therefore considered to be important...... oscillations in intracellular Ca2+ concentrations. However, circulating levels of LIF are not increased with exercise suggesting that LIF exerts its effect locally. LIF stimulates muscle satellite cell proliferation and is involved in muscle hypertrophy and regeneration. Thus, LIF may be produced by skeletal...... contributing factors in muscle homeostasis and muscle adaptation to exercise training. Leukaemia inhibitory factor (LIF) is produced and released from muscle cells in vitro and from intact skeletal muscle in vivo. During exercise, skeletal muscle potently up-regulates LIF mRNA expression, likely due to...

  7. Investigation of spacial clustering of rare diseases: childhood malignancies in North Humberside

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, F.; Cartwright, R.; McKinney, P.A.; Ricketts, T.J. (Leukaemia Research Fund Centre for Clinical Epidemiology, Leeds (UK))

    1990-03-01

    The study aims were (1) to test for uniformity of distribution of childhood leukaemias and other malignancies; and (2) to consider aetiological implications of unusual distributions. 144 children under 15 years old with a diagnosis of malignant disease known to the Yorkshire Regional Chilhood Tumour Registry between 1974 and 1986 were included in the analysis. Of these 53 had leukaemias and nine lymphomas. Significant localised clustering was found in North Humberside, though not in the whole Yorkshire Health Region. A number of clustered cases were identified, some of whom were in a post code sector, Hull 10 to the west of Kingston-upon-Hull, about which concern had been expressed since 1985. There was however no evidence that disease clustering was confined to this area. Four previously suggested hypotheses about causation in this area were examined but results were negative or inconclusive. (author).

  8. SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance

    DEFF Research Database (Denmark)

    Cruickshank, V Adam; Sroczynska, Patrycja; Sankar, Aditya;

    2015-01-01

    tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the...... selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the...

  9. Childhood Obesity

    Science.gov (United States)

    Yuca, Sevil Ari, Ed.

    2012-01-01

    This book aims to provide readers with a general as well as an advanced overview of the key trends in childhood obesity. Obesity is an illness that occurs due to a combination of genetic, environmental, psychosocial, metabolic and hormonal factors. The prevalence of obesity has shown a great rise both in adults and children in the last 30 years.…

  10. Childhood Obesity

    Centers for Disease Control (CDC) Podcasts

    2013-08-06

    In this podcast, Dr. Tom Frieden, CDC Director, discusses the decrease in childhood obesity rates and what strategies have been proven to work to help our children grow up and thrive.  Created: 8/6/2013 by National Center for Injury Prevention and Control.   Date Released: 3/6/2014.

  11. Childhood obesity.

    Science.gov (United States)

    Strauss, R

    1999-01-01

    Approximately 10% of children are obese. Twin and adoption studies demonstrate a large genetic component to obesity, especially in adults. However, the increasing prevalence of obesity over the last 20 years can only be explained by environmental factors. In most obese individuals, no measurable differences in metabolism can be detected. Few children engage in regular physical activity. Obese children and adults uniformly underreport the amount of food they eat. Obesity is particularly related to increased consumption of high-fat foods. BMI is a quick and easy way to screen for childhood obesity. Treating childhood obesity relies on positive family support and lifestyle changes involving the whole family. Food preferences are influenced early by parental eating habits, and when developed in childhood, they tend to remain fairly constant into adulthood. Children learn to be active or inactive from their parents. In addition, physical activity (or more commonly, physical inactivity) habits that are established in childhood tend to persist into adulthood. Weight loss is usually followed by changes in appetite and metabolism, predisposing individuals to regain their weight. However, when the right family dynamics exist--a motivated child with supportive parents--long-term success is possible.

  12. Chemotherapy in a transplantable myeloid leukaemia in brown Norway rats : studies on BNML as a model for human acute myeloid leukaemia

    NARCIS (Netherlands)

    L.P. Colly

    1980-01-01

    textabstractLeukaemia accounts for less than 5% of the total number of malignant diseases in the USA {McCredie et al., 1976),· while about 9% of all neeplasros in the Netherlands originate in the lymphatic and blood forming organs. Because of the relatively easy accessibility of the turnoor cells in

  13. Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M;

    1999-01-01

    -impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region...

  14. Childhood vitiligo

    Directory of Open Access Journals (Sweden)

    Aparna Palit

    2012-01-01

    Full Text Available Childhood vitiligo is often encountered in dermatological practice. When present in infancy or early childhood, various nevoid and hereditary disorders are to be differentiated. In many cases, familial aggregation of the disease is seen and other autoimmune disorders may be associated. Segmental presentation is more common, and limited body surface area involvement is usual in this age group. Children with vitiligo often suffer from anxiety and depression because of their unusual appearance. Management of vitiligo in children is difficult as therapeutic options are restricted when compared to that in adult patients. Selection of treatment should be careful in these patients with the aim to achieve best results with minimal side effects as well as relieving patients′ and parents′ anxiety.

  15. Childhood psoriasis

    OpenAIRE

    Dogra Sunil; Kaur Inderjeet

    2010-01-01

    Psoriasis is a common dermatosis in children with about one third of all patients having onset of disease in the first or second decade of life. A chronic disfiguring skin disease, such as psoriasis, in childhood is likely to have profound emotional and psychological effects, and hence requires special attention. Psoriasis in children has been reported to differ from that among adults being more frequently pruritic; plaque lesions are relatively thinner, softer, and less scaly; face and flexu...

  16. Childhood pancreatitis.

    Science.gov (United States)

    Uretsky, G; Goldschmiedt, M; James, K

    1999-05-01

    Acute pancreatitis is a rare finding in childhood but probably more common than is generally realized. This condition should be considered in the evaluation of children with vomiting and abdominal pain, because it can cause significant morbidity and mortality. Clinical suspicion is required to make the diagnosis, especially when the serum amylase concentration is normal. Recurrent pancreatitis may be familial as a result of inherited biochemical or anatomic abnormalities. Patients with hereditary pancreatitis are at high risk for pancreatic cancer.

  17. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; Kooy, Marinus van Marwijk; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Boer, Fransien Croon-de; Eefting, Matthijs; Jie, Kon-Siong G.; de Loosdrecht, Arjan A. van; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  18. Childhood Traumatic Grief

    Science.gov (United States)

    ... Educators Resources for Kids and Teens Childhood Traumatic Grief What is Childhood Traumatic Grief? Children grieve in their own way following the ... child may have a condition called Childhood Traumatic Grief (CTG). Thinking about the person who died—even ...

  19. Childhood Cancer Statistics

    Science.gov (United States)

    ... Shop With CureSearch Blog Donate Now Select Page Childhood Cancer Statistics Home > Understanding Children’s Cancer > Childhood Cancer Statistics Childhood Cancer Statistics – Graphs and Infographics Number of Diagnoses ...

  20. Hospital contacts for endocrine disorders in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): a population-based cohort study

    DEFF Research Database (Denmark)

    de Fine Licht, Sofie; Winther, Jeanette Falck; Gudmundsdottir, Thorgerdur;

    2014-01-01

    BACKGROUND: The pattern of endocrine disorders in long-term survivors of childhood cancer has not been investigated comprehensively. Here, we aimed to assess the lifetime risk of these disorders in Nordic survivors of childhood cancer. METHODS: From the national cancer registries of Denmark...... were linked to the national hospital registries, and observed numbers of first-time hospital contacts for endocrine disorders in survivors of childhood cancer were compared with the expected numbers derived from the population comparison cohort. We calculated the absolute excess risks attributable...... to status as a childhood cancer survivor and standardised hospitalisation rate ratios (SHRRs). FINDINGS: Of the childhood cancer survivors, 3292 had contact with a hospital for an endocrine disorder, yielding a SHRR of 4·8 (95% CI 4·6-5·0); the highest risks were in survivors of leukaemia (SHRR 7·3 [95% CI...

  1. Granulocytic sarcoma of the femur in a patient with acute megakaryoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Čolović Milica

    2011-01-01

    Full Text Available Introduction. Granulocytic sarcoma, chloroma or myeloblastoma are observed in 3% to7% of acute myeloid leukaemia and represents localized tumour composed of collection of immature leukaemic cells. It appears most frequently in patients with M2, M4 and M5 subtypes of acute myeloid leukaemia Case Outline. A 58-year-old female presented with pain and oedema of the right upper limb in November 2009. After two months the patinet had fracture dislocation and numerous osteolytic lesions of the right femur. Immunohistochemistry of tumour biopsy showed megakaryoblastic granulocytic sarcoma which was CD31++, F-XIII++, CD34-, FVIII+++, S100-, aktin-, EMA++, Bcl2++, CD43++, with positive proliferative marker measured with Ki-67 positivity in more of 50% of cells. Aspirate of bone marrow and immunophenotyping with flowcytometry revealed diagnosis of acute megakaryoblastic leukaemia. The course of the disease was rapid and the patient died before commencing chemotherapy, five months after first complaints. Conclusion. Granulocytic sarcoma is extramedullary localization of collection of leukaemia cells which can proceed, to arise concomitantly with leukaemia, or may be the only manifestation of the disease. The diagnosis can be established only with immunohystochemistry.

  2. Living with the Diagnosis and Treatment of Leukaemia in a Child with Down's Syndrome: A Mother's Reflection

    Science.gov (United States)

    Self, Donna

    2008-01-01

    In this article I will discuss the impact of my 2-year-old son's diagnosis and treatment of leukaemia. I will outline the background to being told he had leukaemia before describing the family dynamics that emerged during this time for me, my husband and our other child. My story will focus on managing the practicalities of a long stay in hospital…

  3. Epidural spinal cord compression as initial clinical presentation of an acute myeloid leukaemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Dominique N'Dri Oka; Alpha Boubacar Bah; André Valentin Tokpa; Louis Derou

    2016-01-01

    Epidural localization of myeloid leukaemia is rarely reported.Spinal cord compression as an initial presentation of acute myeloid leukaemia is extremely rare.This is a report of a 17-year-old black boy who presented to emergency department with neurological symptoms of spinal cord compression.Imaging modalities showed multiple soft tissue masses in the epidural space.After surgical treatment,histopathological examination of the epidural mass showed myeloid leukaemia cells infiltration.Literature review on Medline and "scholar Google" database was done.The characteristics and management of extra-medullary leukaemia are discussed.Granulocytic sarcoma,myeloid sarcoma or chloroma with acute myeloid leukaemia should be considered as part of epidural spinal cord compression.Therefore surgery is indicated on an emergent basis.

  4. 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.

  5. A Hypothetical-Mathematical Model of Acute Myeloid Leukaemia Pathogenesis

    Directory of Open Access Journals (Sweden)

    Andrei Cucuianu

    2010-01-01

    Full Text Available Acute myeloid leukaemia is defined by the expansion of a mutated haematopoietic stem cell clone, with the inhibition of surrounding normal clones. Haematopoiesis can be seen as an evolutionary tree, starting with one cell that undergoes several divisions during the expansion phase, afterwards losing functional cells during the aging-related contraction phase. During divisions, offspring cells acquire ‘variations’, which can be either normal or abnormal. If an abnormal variation is present in more than 25% of the final cells, a monoclonal, leukemic pattern occurs. Such a pattern develops if: (A1 The abnormal variation occurs early, during the first or second divisions; (A2 The variation confers exceptional proliferative capacity; (B A sizable proportion of the normal clones are destroyed and a previously non-significant abnormal clone gains relative dominance over a depleted environment; (C The abnormal variation confers relative ‘immortality’, rendering it significant during the contraction phase. Combinations of these pathways further enhance the leukemic risk of the system. A simple mathematical model is used in order to characterize normal and leukemic states and to explain the above cellular processes generating monoclonal leukemic patterns.

  6. Clofarabine in the treatment of poor risk acute myeloid leukaemia.

    LENUS (Irish Health Repository)

    Krawczyk, Janusz

    2010-09-01

    Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.

  7. A Ten Year Descriptive Study of Adult Leukaemia at Al-Jomhori Teaching Hospital in Sana'a, Yemen

    Directory of Open Access Journals (Sweden)

    Jameel Al-Ghazaly

    2014-12-01

    Full Text Available Background: There is scarcity of data of the epidemiology of leukaemia in Arab countries including Yemen. Understanding patterns of leukaemia underpins epidemiology and can provide insight into disease etiology. The aim of this research is to determine the epidemiologic pattern of adult leukaemia in Yemen. Methods: The research is a descriptive cross-sectional study. We analyzed the data of 702 adult patients with leukaemia, who were newly diagnosed over a ten-year period between October 1999 and October 2009 at the referral haematology centre in Sana’a at Al-Jomhori Teaching Hospital, according to type of leukaemia, age, sex, geographic distribution and time of diagnosis. Results: Acute Myeloid Leukaemia (AML was found to be the most common (45.1% followed by Chronic Myeloid Leukaemia (CML (26.5%, Acute Lymphoid Leukaemia (ALL (17.7% and Chronic Lymphoid Leukaemia (CLL (10.7%, respectively. There was an almost equal prevalence of AML and CML for males and females but males had significantly more cases of ALL and CLL (p =0.008. A significant variation in geographic pattern showed that the highest number of cases is seen the Central mountainous region and the least number of cases in the South-eastern region which is coastal and lowland (p<0.001. The seasonal variation showed that higher number of ALL cases was seen in the summer months (33% compared with other seasons (21% in the spring, 24.2% in autumn and 21.8% in winter. Conclusions: The pattern of adult leukaemia in Yemen is different from that seen in western countries which could be attributed to different environmental exposure. The geographic pattern indicates a possible role of certain environmental factors which warrant further investigations. The pattern of seasonal variation needs further studies for evaluating the seasonality.

  8. Childhood psoriasis

    Directory of Open Access Journals (Sweden)

    Dogra Sunil

    2010-01-01

    Full Text Available Psoriasis is a common dermatosis in children with about one third of all patients having onset of disease in the first or second decade of life. A chronic disfiguring skin disease, such as psoriasis, in childhood is likely to have profound emotional and psychological effects, and hence requires special attention. Psoriasis in children has been reported to differ from that among adults being more frequently pruritic; plaque lesions are relatively thinner, softer, and less scaly; face and flexural involvement is common and guttate type is the characteristic presentation. Whether onset in childhood predicts a more severe form of psoriasis is a matter of controversy, it may cause significant morbidity particularly if it keeps relapsing. Most children have mild form of psoriasis which can be generally treated effectively with topical agents such as emollients, coal tar, corticosteroids, dithranol, calcipotriol etc. according to age and the sites affected. Narrow band UVB is the preferred form of phototherapy in children for moderate to severe disease or in patients not responding to topical therapy alone. Systemic therapies are reserved for more severe and extensive cases that cannot be controlled with topical treatment and/or phototherapy such as severe plaque type, unstable forms like erythrodermic and generalized pustular psoriasis and psoriatic arthritis. There are no controlled trials of systemic therapies in this age group, most experience being with retinoids and methotrexate with favorable results. Cyclosporine can be used as a short-term intermittent crisis management drug. There is an early promising experience with the use of biologics (etanercept and infliximab in childhood psoriasis. Systemic treatments as well as phototherapy have limited use in children due to cumulative dose effects of drugs, low acceptance, and risk of gonadal toxicity. More evidence-based data is needed about the effectiveness and long-term safety of topical

  9. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...... bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction...

  10. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Morgulis Yuri

    2012-05-01

    Full Text Available Abstract Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

  11. Childhood cancer and exposure to corona ions from power lines: an epidemiological test

    International Nuclear Information System (INIS)

    We previously reported an association between childhood leukaemia in Britain and proximity of the child’s address at birth to high-voltage power lines that declines from the 1960s to the 2000s. We test here whether a ‘corona-ion hypothesis’ could explain these results. This hypothesis proposes that corona ions, atmospheric ions produced by power lines and blown away from them by the wind, increase the retention of airborne pollutants in the airways when breathed in and hence cause disease. We develop an improved model for calculating exposure to corona ions, using data on winds from meteorological stations and considering the whole length of power line within 600 m of each subject’s address. Corona-ion exposure is highly correlated with proximity to power lines, and hence the results parallel the elevations in leukaemia risk seen with distance analyses. But our model explains the observed pattern of leukaemia rates around power lines less well than straightforward distance measurements, and ecological considerations also argue against the hypothesis. This does not disprove the corona-ion hypothesis as the explanation for our previous results, but nor does it provide support for it, or, by extension, any other hypothesis dependent on wind direction. (paper)

  12. Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Pal, D; Blair, H J; Elder, A; Dormon, K; Rennie, K J; Coleman, D J L; Weiland, J; Rankin, K S; Filby, A; Heidenreich, O; Vormoor, J

    2016-08-01

    Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction. Moreover, surface expression of adhesion molecules CD34, CDH2 and CD10 increased several fold. Approximately 20% of the ALL cells were in G0 phase of the cell cycle, suggesting that MSCs may support quiescent ALL cells. Cellular barcoding demonstrated long-term preservation of clonal abundance. Expansion of ALL cells for >3 months compromised neither feeder dependence nor cancer initiating ability as judged by their engraftment potential in immunocompromised mice. Finally, we demonstrate the suitability of this co-culture approach for the investigation of drug combinations with luciferase-expressing primograft ALL cells. Taken together, we have developed a preclinical platform with patient-derived material that will facilitate the development of clinically effective combination therapies for ALL.

  13. The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Janowski, M. (Centre d' Etude de l' Energie Nucleaire, Mol (Belgium)); Cox, R. (Medical Research Council, Harwell (UK). Radiobiological Research Unit); Strauss, P.G. (GSF, Neuherberg (Germany, F.R.). Abt. fuer Molekulare Zellpathologie)

    1990-04-01

    In mice, external X- or {gamma}-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking {alpha}-emitters may induce osteosarcomas, and to a lesser extent acute myeloid leukaemia. The paper reviews briefly some experimental data in respect to molecular mechanisms underlying these radio-carcinogenic processes. Thymic lymphomagenesis proceeds by an indirect mechanism in which recombinant proviruses could be involved. Myeloid leukaemogenesis is characterized by a very early putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumors often contain somatically acquired proviruses. (UK).

  14. 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.

  15. Childhood psoriasis.

    Science.gov (United States)

    Farber, E M; Nall, L

    1999-11-01

    Psoriasis is a common skin disease in infants, children, and adolescents. A review of the clinical, epidemiologic, genetic, and therapeutic aspects of childhood psoriasis is presented. Population studies indicate that the first signs of psoriatic lesions occur in the pediatric age group, birth to 18 years of age, and that both genetic and environmental factors interact to precipitate the development of psoriasis. Koebner reactions are the result of external or internal triggering factors, such as physical injury to the skin, low humidity, and certain drugs. The most frequently observed variant to psoriasis is the plaque type, followed by guttate psoriasis, and juvenile psoriatic arthritis. Pustular psoriasis and erythrodermic psoriasis are rare forms of the disease, but are seen in children from infancy to adolescence. The scalp is the most frequently affected site of involvement in pediatric psoriasis, followed by the appearance of lesions on the extensor surfaces of the extremities, trunk, and nails. Although not common in adult psoriasis, the face and ears are often involved. Topical medications such as corticosteroids, calcipotriol, coal tar preparations, anthralin formulations, and ultraviolet B are recommended in monotherapy or in combination therapy, whereas psoralen plus ultraviolet A, methotrexate, and retinoids should only be administered in crisis situations. The treatment objectives in childhood psoriasis are to preserve skin surfaces, to afford physical relief from the disease, and to employ treatments that do not endanger the health or future development of the child.

  16. Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

    International Nuclear Information System (INIS)

    A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incident at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy. (Author)

  17. Radiation-induced acute myeloid leukaemia in mice

    International Nuclear Information System (INIS)

    Ample epidemiological studies of human populations implicate ionizing radiation as a carcinogen and these quantitative studies provide the foundation for the core estimates of radiation cancer risk. The majority of the epidemiological data originate from situations of radiation exposure at high dose and high dose rate. The relevance of risk estimates based on such exposures to the more commonly encountered low dose and dose rate situation has been questioned frequently. Thus, there is a need to investigate and quantitate low dose and dose rate effects. A number of approaches may be considered, for example, very large scale epidemiology, very large scale animal experimentation; however, both of these present problems of a practical and/or ethical nature. A further possible approach is that of mechanistic modelling. This requires a fairly detailed understanding of neoplastic disease and how it develops post-irradiation. Many factors and variables have to be taken into consideration in mechanistic modelling approaches. Testing of mechanistic modelling schemes is best carried out using animal model systems. Acute myeloid leukaemia (AML) is a radiogenic cancer of significance in man and several good mouse models of the disease are available. Here, recent studies conducted at NRPB with the aim of elucidating the post-irradiation development of AML will be discussed. In particular three areas critical for developing a sound mechanistic model will be covered, definition of the initiating event; study of disease progression, this addresses the question of the frequency of conversion of initiated cells into the neoplastic state and the influence of genetic background on leukaemogenesis. (author)

  18. Detection of transient and persistent feline leukaemia virus infections.

    Science.gov (United States)

    Jarrett, O; Golder, M C; Stewart, M F

    1982-03-01

    A study was made of cats persistently or transiently viraemic with feline leukaemia virus (FeLV) following experimental oronasal infection. Cats of two ages were exposed to the virus. One group was infected when eight weeks old in the expectation that most of the cats would become persistently viraemic, and the second group when 16 weeks old, so that some would show signs of a transient infection and then recover. The periods following infection when virus was detectable in the blood and in the oropharynx were determined for each group. Three methods for detecting viraemia were compared: virus isolation, immunofluorescence on blood smears and an enzyme-linked immunosorbent assay (ELISA). There was good overall agreement among the three tests in detecting virus-positive cats. Virus was found sooner after infection by virus isolation than by the other methods, and virus appeared in the blood slightly sooner in cats which developed persistent viraemia than in transiently viraemic cats. Infectious FeLV was isolated from the oropharynx of all of the persistently viraemic cats, in most cases simultaneously with virus in the plasma. Virus was also isolated from the mouth of most transiently viraemic cats. Under field conditions such transient excretion of virus lasting only a few days would rarely be detected in a single sampling. This might explain how FeLV is maintained in free range urban cats in the absence of a large number of cats with persistent active FeLV infection. For routine diagnosis, immunofluorescence would appear to offer the best chance of differentiating transient and persistent infections by FeLV.

  19. Childhood cancer mortality in relation to the St Lucie nuclear power station

    International Nuclear Information System (INIS)

    An unusual county-wide excess of childhood cancers of brain and other nervous tissue in the late 1990s in St Lucie County, Florida, prompted the Florida Department of Health to conduct a case-control study within the county assessing residential chemical exposures. No clear associations were found, but claims were then made that the release of radioactive substances such as strontium 90 from the St Lucie nuclear power station, which began operating in 1976, might have played a role. To test the plausibility of this hypothesis, we extended by 17 years a previous study of county mortality conducted by the National Cancer Institute. Rates of total cancer, leukaemia and cancer of brain and other nervous tissue in children and across all ages in St Lucie County were evaluated with respect to the years before and after the nuclear power station began operation and contrasted with rates in two similar counties in Florida (Polk and Volusia). Over the prolonged period 1950-2000, no unusual patterns of childhood cancer mortality were found for St Lucie County as a whole. In particular, no unusual patterns of childhood cancer mortality were seen in relation to the start-up of the St Lucie nuclear power station in 1976. Further, there were no significant differences in mortality between the study and comparison counties for any cancer in the time period after the power station was in operation. Relative rates for all childhood cancers and for childhood leukaemia were higher before the nuclear facility began operating than after, while rates of brain and other nervous tissue cancer were slightly lower in St Lucie County than in the two comparison counties for both time periods. Although definitive conclusions cannot be drawn from descriptive studies, these data provide no support for the hypothesis that the operation of the St Lucie nuclear power station has adversely affected the cancer mortality experience of county residents

  20. Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow

    International Nuclear Information System (INIS)

    Haemopoietic radiation chimeras across the H-2 barrier (BALB/c → C57B1/6; H-2sup(d) → H-2sup(b) chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57B1/6 mice was injected i.p. into established chimeras (H-2sup(d) → H-2sup(b)). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c → C57B1/6 or C57B1/6 → BALB/c chimeras. However, inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c → C57B1/6 chimeras failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2sup(d) → H-2sup(b) chimeras displayed complete resistance to inoculation of leukaemogenic H-2sup(b) restricted RadLV while all H-2sup(b) → H-2sup(b), syngeneically reconstituted mice developed disseminated leukaemia. (author)

  1. Investigation of the possible increased incidence of leukaemia in young people near the Dounreay Nuclear Establishment, Caithness, Scotland. 2. report

    International Nuclear Information System (INIS)

    A report is given by the Committee on Medical Aspects of Radiation in the Environment investigating the possible increased incidence of leukaemia in young people near the Dounreay Nuclear Establishment in Scotland. After describing the environment in which the site is situated, subsequent chapters examine the known epidemiological data available on leukaemia incidence in young people in the area, the radioactive discharges and the radiation doses to the population calculated from these discharges and recommendations for further studies. On present knowledge, the report is unable to ascribe the observed incidence of leukaemia to specific causes. (U.K.)

  2. Two consecutive immunophenotypic switches in a child with immunogenotypically stable acute leukaemia

    NARCIS (Netherlands)

    Bierings, M; Szczepanski, T; van Wering, ER; Willemse, MJ; Langerak, AW; Revesz, T; van Dongen, JJM

    2001-01-01

    A 12-year-old girl presented with a CD33(+) precursor B-acute lymphoblastic leukaemia (ALL) and seemed to respond well to ALL treatment. However. 2 weeks after diagnosis her leucocyte count rose rapidly with a predominance of myeloid blasts with M5b morphology and CD19(+) myeloid immunophenotype. Ac

  3. Effect of glutathione S-transferases on the survival of patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Autrup, Judith; Hokland, Peter; Pedersen, Lars;

    2002-01-01

    The objective of the study was to investigate the effect of genetic polymorphisms in glutathione S-transferases (GST) on the survival of acute myeloid leukaemia patients receiving adriamycin induction therapy. A total of 89 patients were included in the study. Patients who carried at least one GSTM...

  4. Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

    DEFF Research Database (Denmark)

    Jethwa, Alexander; Hüllein, Jennifer; Stolz, Tatjana;

    2013-01-01

    Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were...

  5. Evaluation of natural transmission of bovine leukaemia virus within dairy herds of Argentina

    NARCIS (Netherlands)

    Monti, G.E.; Frankena, K.; Jong, de M.C.M.

    2007-01-01

    The purpose of this study was to describe patterns of seroconversion to bovine leukaemia virus and to estimate the main parameters needed for future model building. A longitudinal study was carried out between February 1999 and November 2001 in seven commercial dairy farms in Argentina using 1535 la

  6. Feedback mechanisms control coexistence in a stem cell model of acute myeloid leukaemia.

    Science.gov (United States)

    Crowell, Helena L; MacLean, Adam L; Stumpf, Michael P H

    2016-07-21

    Haematopoietic stem cell dynamics regulate healthy blood cell production and are disrupted during leukaemia. Competition models of cellular species help to elucidate stem cell dynamics in the bone marrow microenvironment (or niche), and to determine how these dynamics impact leukaemia progression. Here we develop two models that target acute myeloid leukaemia with particular focus on the mechanisms that control proliferation via feedback signalling. It is within regions of parameter space permissive of coexistence that the effects of competition are most subtle and the clinical outcome least certain. Steady state and linear stability analyses identify parameter regions that allow for coexistence to occur, and allow us to characterise behaviour near critical points. Where analytical expressions are no longer informative, we proceed statistically and sample parameter space over a coexistence region. We find that the rates of proliferation and differentiation of healthy progenitors exert key control over coexistence. We also show that inclusion of a regulatory feedback onto progenitor cells promotes healthy haematopoiesis at the expense of leukaemia, and that - somewhat paradoxically - within the coexistence region feedback increases the sensitivity of the system to dominance by one lineage over another. PMID:27130539

  7. 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

  8. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats...

  9. Leukaemia and occupation: a New Zealand Cancer Registry-based case-control Study.

    NARCIS (Netherlands)

    McLean, D.; 't Mannetje, A.; Dryson, E.; Walls, C.; McKenzie, F.; Maule, M.; Cheng, S.; Cunningham, C.; Kromhout, H.; Boffetta, P.; Blair, A.; Pearce, N.

    2009-01-01

    BACKGROUND: To examine the association between occupation and leukaemia. METHODS: We interviewed 225 cases (aged 20-75 years) notified to the New Zealand Cancer Registry during 2003-04, and 471 controls randomly selected from the Electoral Roll collecting demographic details, information on potentia

  10. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse

    NARCIS (Netherlands)

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel-Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valerie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.

    2014-01-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n

  11. Studies on the role of RNA tumour viruses in human leukaemia

    International Nuclear Information System (INIS)

    A search has been made for an etiological role of retroviruses in human leukemia and cocultivation studies have led to the isolation of a presumed human type C virus which appeared to be oncogenic for experimental animals. The experimental procedures and results are fully discussed. The parallels between irradiation induced lymphomas in mice and leukaemias in man are explored. (C.F.)

  12. Feasibility of neuropsychological assessment in leukaemia patients shortly after diagnosis : directions for future prospective research

    NARCIS (Netherlands)

    Jansen, NC; Kingma, A; Tellegen, P; van Dommelen, RI; Bouma, A; Veerman, A; Kamps, WA

    2005-01-01

    Aims: To study neuropsychological functioning of newly diagnosed children with acute lymphoblastic leukaemia (ALL) within two weeks after diagnosis in order to determine the feasibility of a sibling controlled prospective study design. Methods: Fifty consecutive patients (median age at testing 6.6 y

  13. Effect of dexamethasone on quality of life in children with acute lymphoblastic leukaemia: a prospective observational study

    Directory of Open Access Journals (Sweden)

    Kaspers Gert Jan L

    2008-11-01

    Full Text Available Abstract Background Glucocorticoids are important in the treatment of childhood acute lymphoblastic leukaemia (ALL. However, cyclic administration of high dose glucocorticoids may cause rapid and substantial changes in quality of life (QoL. The maintenance phase of the Dutch ALL-9 protocol consisted of alternating two weeks on and five weeks off dexamethasone (6 mg/m2/day. The present study was performed to assess the effect of dexamethasone on QoL during treatment for ALL according to this protocol. Methods In a multicentre prospective cohort study, QoL was assessed halfway (T1 and at the end of the two-year treatment (T2. A generic (Child Health Questionnaire and disease specific (PedsQL™ cancer version QoL questionnaire were used to assess QoL in two periods: on and off dexamethasone, respectively. Results 41 children (56% males were evaluated, mean age at diagnosis was 5.6 years. The CHQ physical and psychosocial summary scores were significantly lower than population norms. At T1 and T2, overall QoL showed no significant change. However, regarding specific domains (pain, cognitive functioning, emotion/behaviour and physical functioning QoL decreased over time. QoL was significantly more impaired during periods on dexamethasone. Conclusion Dexamethasone was associated with decreased QoL. At the end of treatment, reported QoL during dexamethasone deteriorated even more on certain scales (pain, cognitive functioning, emotion/behaviour and physical functioning. Knowledge of the specific aspects of QoL is essential to improve counselling and coping in paediatric oncology. Adverse effects of specific drugs on QoL should be taken into account when designing treatment protocols.

  14. Childhood medulloblastoma.

    Science.gov (United States)

    Massimino, Maura; Biassoni, Veronica; Gandola, Lorenza; Garrè, Maria Luisa; Gatta, Gemma; Giangaspero, Felice; Poggi, Geraldina; Rutkowski, Stefan

    2016-09-01

    Medulloblastoma accounts for 15-20% of childhood nervous system tumours. The risk of dying was reduced by 30% in the last twenty years. Patients are divided in risk strata according to post-surgical disease, dissemination, histology and some molecular features such as WNT subgroup and MYC status. Sixty to 70% of patients older than 3 years are assigned to the average-risk group. High-risk patients include those with disseminated and/or residual disease, large cell and/or anaplastic histotypes, MYC genes amplification. Current and currently planned clinical trials will: (1) evaluate the feasibility of reducing both the dose of craniospinal irradiation and the volume of the posterior fossa radiotherapy (RT) for those patients at low biologic risk, commonly identified as those having a medulloblastoma of the WNT subgroup; (2) determine whether intensification of chemotherapy (CT) or irradiation can improve outcome in patients with high-risk disease; (3) find target therapies allowing tailored therapies especially for relapsing patients and those with higher biological risk. PMID:27375228

  15. Importance of genotyping of Thiopurine S-methyltransferase in children with acute lymphoblastic leukaemia during maintenance therapy

    Directory of Open Access Journals (Sweden)

    Dokmanović Lidija

    2008-01-01

    Full Text Available INTRODUCTION Thiopurine S-methyltransferase (TPMT is an enzyme that catalyses the inactivation of mercaptopurine (MP which is widely used in the treatment of acute lymphoblastic leukaemia (ALL of childhood. Potentially fatal myelotoxicity may develop after standard doses of MP in TPMT deficient patients. OBJECTIVES To establish if individually tailored doses of MP can reduce myelotoxicity in ALL patients carrying mutations in the TPMT gene. To establish if variable number of tandem repeats (VNTR genotype influences the treatment effects of MP. METHOD Fifty randomly selected patients treated according to ALL IC-BFM 2002 protocol were tested for most frequent TPMT gene mutations using PCR based methods. VNTR genotype was determined in 20 children by PCR methods. During the maintenance phase, we recorded the number of weeks when therapy was applied in either full doses, reduced doses or when patients were without any therapy. RESULTS Fifty children were examined, 29 boys (58% and 21 girls (42%; age ranged from 1.8-17.3 years (median 6.2 years. Four patients (8% were heterozygous for TPMT mutations, all of them carrying the TPMT*3A variant. After 12, 14, 16 and 19 weeks of therapy with reduced doses of MP, the patients switched to full doses due to good tolerance. There was no therapy omission. Cumulative dose of MP was reduced for 7.8%, 7.4%, 11.2% and 16.6%, respectively, in patients with TPMT mutations. No significant difference was found between children with no mutations and TPMT heterozygotes regarding full dose therapy (53.6 vs. 55.7 weeks, respectively and reduced dose therapy (19.9 vs. 15.2 weeks respectively. The number of detected VNTRs ranged from four to seven. The majority of patients had different number of VNTRs on homologous chromosomes. Most frequently detected polymorphism was VNTR*5. No correlation was found between TPMT and VNTR genotype inheritance. CONCLUSION Obeying pharmacogenetic principles in the treatment of childhood ALL

  16. Autoimmune diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS)

    DEFF Research Database (Denmark)

    Holmqvist, Anna Sällfors; Olsen, Jørgen H.; Mellemkjaer, Lene;

    2015-01-01

    all autoimmune diseases combined, corresponding to an AER of 67 per 100 000 person-years. The SHRRs were significantly increased for autoimmune haemolytic anaemia (16.3), Addison's disease (13.9), polyarteritis nodosa (5.8), chronic rheumatic heart disease (4.5), localised scleroderma (3......OBJECTIVES: The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries.......6), idiopathic thrombocytopenic purpura (3.4), Hashimoto's thyroiditis (3.1), pernicious anaemia (2.7), sarcoidosis (2.2), Sjögren's syndrome (2.0) and insulin-dependent diabetes mellitus (1.6). The SHRRs for any autoimmune disease were significantly increased after leukaemia (SHRR 1.6), Hodgkin's lymphoma (1...

  17. Childhood Overweight and Obesity

    Science.gov (United States)

    ... Childhood Obesity Facts The prevalence of obesity among low-income children aged 2 through 4 years, by state ... Obesity now affects 1 in 6 children and adolescents in the United States. Childhood Obesity Facts How ...

  18. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  19. French “real life” experience of clofarabine in children with refractory or relapsed acute lymphoblastic leukaemia

    OpenAIRE

    Trioche, Pascale; Nelken, Brigitte; Michel, Gérard; Pellier, Isabelle; Petit, Arnaud; Bertrand, Yves; Rohrlich, Pierre; Schmitt, Claudine; Sirvent, Nicolas; Boutard, Patrick; Margueritte, Geneviève; Pautard, Brigitte; Ducassou, Stéphane; Plantaz, Dominique; Robert, Alain

    2012-01-01

    Background Clofarabine alone or in combination with cyclophosphamide and etoposide has shown a good efficacy and a tolerable toxicity profile in previous studies of children with relapsed or refractory leukaemia. This report describes a retrospective study of 38 French patients who received clofarabine as a monotherapy or in combination for relapsed or refractory acute lymphoblastic leukaemia (ALL) outside of clinical trials after marketing authorization. Methods We retrospectively analysed d...

  20. Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group.

    OpenAIRE

    Bennett, J M; Catovsky, D.; Daniel, M T; Flandrin, G; Galton, D A; Gralnick, H R; Sultan, C.

    1989-01-01

    Peripheral blood, bone marrow films, and bone marrow biopsy specimens from 110 patients, well characterised by clinical and laboratory studies, including electron microscopy, were reviewed, to determine proposals for the classification of chronic (mature) B and T cell leukaemias. On the basis of cytology and membrane phenotype the following disorders were defined: (i) B cell type: chronic lymphocytic leukaemia (CLL); CLL of mixed cell type, which includes cases with more than 10% and less tha...

  1. MLL-rearranged acute lymphoblastic leukaemia stem cell interactions with bone marrow stroma promote survival and therapeutic resistance that can be overcome with CXCR4 antagonism

    OpenAIRE

    Sison, Edward Allan R; Rau, Rachel E.; McIntyre, Emily; LI Li; Small, Donald; Brown, Patrick

    2013-01-01

    Infants with MLL-rearranged (MLL-R) acute lymphoblastic leukaemia (ALL) have a dismal prognosis. While most patients achieve remission, approximately half of patients recur with a short latency to relapse. This suggests that chemotherapy-resistant leukaemia stem cells (LSCs) survive and can recapitulate the leukaemia. We hypothesized that interactions between LSCs and the bone marrow microenvironment mediate survival and chemotherapy resistance in MLL-R ALL. Using primary samples of infant ML...

  2. Magnetic fields and childhood cancer: an epidemiological investigation of the effects of high-voltage underground cables.

    Science.gov (United States)

    Bunch, K J; Swanson, J; Vincent, T J; Murphy, M F G

    2015-09-01

    Epidemiological evidence of increased risks for childhood leukaemia from magnetic fields has implicated, as one source of such fields, high-voltage overhead lines. Magnetic fields are not the only factor that varies in their vicinity, complicating interpretation of any associations. Underground cables (UGCs), however, produce magnetic fields but have no other discernible effects in their vicinity. We report here the largest ever epidemiological study of high voltage UGCs, based on 52,525 cases occurring from 1962-2008, with matched birth controls. We calculated the distance of the mother's address at child's birth to the closest 275 or 400 kV ac or high-voltage dc UGC in England and Wales and the resulting magnetic fields. Few people are exposed to magnetic fields from UGCs limiting the statistical power. We found no indications of an association of risk with distance or of trend in risk with increasing magnetic field for leukaemia, and no convincing pattern of risks for any other cancer. Trend estimates for leukaemia as shown by the odds ratio (and 95% confidence interval) per unit increase in exposure were: reciprocal of distance 0.99 (0.95-1.03), magnetic field 1.01 (0.76-1.33). The absence of risk detected in relation to UGCs tends to add to the argument that any risks from overhead lines may not be caused by magnetic fields. PMID:26344172

  3. Childhood proptosis

    International Nuclear Information System (INIS)

    Proptosis in children is a hallmark of orbital diseases which can present a diagnostic challenge requiring thoughtful investigation. The aim of this review is to provide the reader an overview of the subject of childhood proptosis with an emphasis on the systematic and practical approach for the work-up of proptosis in children. Use of proper imaging studies is essential for the correct diagnosis. Computed tomography is a good screening test for any space occupying lesion of the orbit. Proptosis describes eye prominence due to space occupying orbital lesions. Congenital lesions usually present in the first decade of life. Acquired orbital lesions such as lymphangiomas, orbital varix, rhabdomyosarcoma and neural tumors may present at the end of the first decade of life. Metastatic tumors to the orbit, adenocarcinoma of lacrimal gland and rapidly growing masses may present with proptosis associated with pain. Visual loss can be the presenting symptoms in the patients with optic nerve (ON) gliomas, orbital meningiomas and posteriorly located tumors. Cystic lesions of the orbit may be congenital or acquired, dermoid cysts being the most common congenital orbital lesions. Some of the vascular lesions of the orbit include capillary hemangiomas, lymphangiomas, orbital varix, and arteriovenous malformations. Inflammatory process of the orbit in children include cellulitis and pseudotumor. Neural tumors such as neurofibromas, ON gilomas and meningiomas are less common causes of proptosis in children. Rhabdomyosarcoma is the most common primary orbital malignancy in children which can present with acute proptosis and is one of the few life-threatening diseases seen initially by an ophthalmologist. Secondary orbital tumors invade the orbit from adjacent sinuses, cranium or extended from the eye itself. The most common distant metastases in children include neuroblastoma and Ewing's sarcoma. Although many orbital processes can be diagnosed based on history, clinical

  4. Treatment-related toxicities in children with acute lymphoblastic leukaemia predisposition syndromes

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld

    2016-01-01

    Although most children with acute lymphoblastic leukaemia (ALL) do not harbor germline mutations that strongly predispose them to development of this malignancy, large syndrome registries and detailed mapping of exomes or whole genomes of familial leukaemia kindreds have revealed that 3-5% of all...... anticancer agents, while others are not. This review summarises our current knowledge on the risk of acute toxicities for these ALL patients and provides guidance for treatment adjustments....... patients is important in order to adjust therapy and offer genetic counseling and cancer surveillance to mutation carriers in the family. In the coming years large genomic screening projects are expected to reveal further hitherto unrecognised familial ALL syndromes. The treatment of ALL cases harboring...

  5. Minor changes on cranial MRI during treatment in children with acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Paeaekkoe, E. [Dept. of Diagnostic Radiology, Univ. of Oulu (Finland); Vainionpaeae, L. [Dept. of Paediatrics, Univ. of Oulu (Finland); Pyhtinen, J. [Dept. of Diagnostic Radiology, Univ. of Oulu (Finland); Lanning, M. [Dept. of Paediatrics, Univ. of Oulu (Finland)

    1996-04-01

    Cranial MRI was used to study treatment-related changes in children undergoing therapy for acute lymphoblastic leukaemia (ALL) or lymphoma. Nineteen children (18 with ALL, 1 with lymphoma) underwent MRI at the beginning of treatment and at intervals during it, to a total of 105 imaging studies and a minimum of 3 per case. Nine patients had finished all therapy, all received consolidation treatment. No patient had central nervous system (CNS) leukaemia at diagnosis or developed a CNS relapse. Mild treatment-related white matter changes were observed in only 2 patients after consolidation therapy with three 5 g/m{sup 2} pulses of intravenous methotrexate. Transient enlargement of the ventricles and cortical sulci was observed in 13 patients, always temporally related to steroid treatment. These preliminary data suggest that treatment-related white matter changes are rare and no routine MRI follow-up is needed during treatment in asymptomatic children after a baseline assessment. (orig.)

  6. Unusual fungal sepsis of Alternaria alternata in acute lymphoblastic leukaemia in an adult patient

    Directory of Open Access Journals (Sweden)

    S Jain

    2015-01-01

    Full Text Available We report a case of unusual fungal sepsis of Alternaria alternata in a patient of acute lymphoblastic leukaemia in 62-year-old male who presented with complaints of 'off and on' fever with decreased oral intake. On evaluation, haemogram showed low platelet count and 68% blast cells in peripheral blood. On flow cytometry of peripheral blood, the gated blasts (approximately 55% highly express CD45, CD10, CD19, CD22 and condition was diagnosed as acute lymphoblastic leukaemia. He was started on standard induction treatment along with supportive therapies. During the course of treatment, two sets of paired blood cultures were sent 48 h apart. All of blood cultures were done on Bac-T alert 3D system. All of them yielded fungus. The fungus was then grown on Sabouraud's Dextrose agar media. It was identified as A. alternata. The patient condition worsened and later had cardiac arrest in ICU and could not be revived.

  7. Femoral diaphyseal stress fracture as the initial presentation of acute leukaemia in an adolescent.

    Science.gov (United States)

    Chase, Helen Emily; Pang, Joe Hwong; Sanghrajka, Anish Pradip

    2016-01-01

    A 14-year-old boy was referred to the orthopaedic clinic by his general practitioner, reporting of a 6-week history of left thigh pain. Clinical examination was unremarkable. Radiographs demonstrated a periosteal reaction at the proximal femur. MRI scans demonstrated a stress fracture of the femur, with no associated sinister features and no evidence of a pathological lesion. As the fracture healed and symptoms improved, the patient became unwell with weight loss, lethargy, chest and jaw pain and fevers. After multiple blood tests over a 25-day period, including five full blood counts and two normal blood films, a third blood film finally demonstrated blasts in keeping with acute leukaemia. We discuss a literature review of musculoskeletal manifestations of leukaemia and the often atypical presentations found. PMID:27353177

  8. Chronic lymphocytic leukaemia: contemporary conceptions of etiology, pathogenesis and peculiarities of clinical manifestations (review

    Directory of Open Access Journals (Sweden)

    Chesnokova N.P.

    2011-06-01

    Full Text Available The research work presents an analysis of literature review and results of investigations on the problems of etiology, pathogenesis, classification and peculiarities of clinical manifestations of chronic lymphocytic leukaemia. Special attention is paid to both contemporary conceptions of carcinogenesis, reflecting the role of proto-oncogenes activation, an-tioncogenes and apoptosis genes suppression in mechanisms of neoplasia development and «specific mechanisms» of oncogenic transformation induction of B-lymphocytes and the subsequent development of the stages of promotion, progression and marked clinical manifestations of formation. Possibility of further improvement of use of immune phe-notype character and oncomarkers in diagnostics of chronic lymphocytic leukaemia clinical variants and in evaluation of effectiveness of its therapy has been indicated in the article

  9. Lower-limb MRI in the staging and re-staging of osteonecrosis in paediatric patients affected by acute lymphoblastic leukaemia after therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ippolito, D.; Masetto, A.; Franzesi, C.T.; Bonaffini, P.A.; Sironi, S. [University of Milano-Bicocca Milan, School of Medicine, Monza (Italy); Department of Diagnostic Radiology, H. San Gerardo, Monza (Italy); Sala, A.; Biondi, A. [University of Milano-Bicocca Milan, School of Medicine, Monza (Italy); H. San Gerardo, Department of Paediatric Haematology, Monza (Italy)

    2016-04-15

    To assess the diagnostic value of MRI examination in detecting and monitoring osteonecrotic lesions (ON) in childhood acute lymphoblastic leukaemia (ALL) after chemotherapy (CHT) and/or bone marrow transplantation (BMT). Seventy-three patients (37 males, mean age 12.4 years old) with ALL after treatment underwent a lower-limb MR examination between November 2006 and March 2012. In 47 there was clinical suspicion of ON, 26 were asymptomatic. Studies were performed with a 1 T and a 1.5 T scanner, acquiring short tau inversion recovery (STIR) and T1-weighted sequences in coronal plane from the hips to the ankles. The average acquisition time was 18 min. Considering baseline and follow-up examinations, the overall number of MRI studies was 195. Fifty-four of 73 patients showed ON at MRI study, with an overall number of 323 ON (89 involving articular surface, 24 with joint deformity, JD). Twenty-five of 47 symptomatic patients showed subchondral ON lesions, 11 developed JD. Three of 26 asymptomatic patients showed subchondral bone ON at baseline examination but no JD at follow-up. Twenty-two of 28 BMT, 32/45 CHT patients developed ON. Our MRI protocol proved to be feasible in evaluating ON in paediatric patients. Studies should be addressed only to symptomatic patients. (orig.)

  10. Activation of NF-ĸB in leukemic cells in response to initial prednisone therapy in children with acute lymphoblastic leukaemia: relation to other prognostic factors.

    Science.gov (United States)

    Kamieńska, Elżbieta; Ociepa, Tomasz; Wysocki, Mariusz; Kurylak, Andrzej; Matysiak, Michał; Urasiński, Tomasz; Urasińska, Elżbieta; Domagała, Wenancjusz

    2011-01-01

    Nuclear factor ĸB (NF-ĸB) is a transcription regulator of proliferation and cell death. Increased activation of NF-ĸB may be responsible for treatment failure in children with acute lymphoblastic leukaemia (ALL). This study aimed to assess changes in NF-ĸB activation in peripheral blood mononuclear cells prior to and after 6 and 12 h of prednisone administration in relation to age, initial WBC count at diagnosis and early treatment response in childhood ALL. The study comprised 55 children with de novo ALL. Cells were stained with mouse anti-NF-ĸB (p65) antibody followed by goat anti-mouse antibody conjugated with FITC and measured by laser scanning cytometer. The nuclear/cytoplasmic (N/C) ratio of NF-ĸB reflecting activation of NF-ĸB was decreased 12 h after treatment in the standard risk group patients, whereas it remained statistically unchanged in the non-standard risk group patients. Changes in the N/C ratio of NF-ĸB were not associated with age and early treatment response; however, in children with an initial WBC count higher than 20 000/μl at diagnosis, this ratio was increased after 6 and 12 h from prednisone administration. The association of higher activation of NF-ĸB with an elevated initial WBC count suggests that activation of NF-ĸB may be responsible for treatment failure in children with ALL. PMID:21574100

  11. Dopamine inhibits proliferation, induces differentiation and apoptosis of K562 leukaemia cells

    Institute of Scientific and Technical Information of China (English)

    HE Qun; YUAN Lin-bo

    2007-01-01

    Background Dopamine exerts its effects mainly in nervous system through D1, D2 or D3 receptors. There are few reports dealing with the effects of dopamine on leukaemia cells. However, some dopamine agonists or antagonists do show biological effects on some types of leukaemia cells. Here, we report the effects of dopamine on the proliferation,differentiation and apoptosis of K562 leukaemia cells.Methods Proliferation was determined by MTT assay and cell counting both in liquid and semisolid cultures.Differentiation was verified by morphology, benzidine staining and flow cytometry. Apoptosis was checked by Hoechst 33258 staining and flow cytometry. The two groups were untreated group and treated group (dopamine 10-9 mol/L-10-4mol/L).Results In liquid culture, MTT assay and colony assay, dopamine inhibited proliferation of K562 cells. Inhibition rate was 29.28% at 10-6 mol/L and 36.10% at 10-5 mol/L after culture for 5 days in MTT assay. In benzidine staining and CD71 expression, dopamine induced K562 cells toward erythroid differentiation by increased 155% at 10-6 mol/L and by 171% at 10-5 mol/L after culture for 5 days in benzidine staining. In Hoechst 33258 staining and flow cytometry,dopamine induced K562 cells toward apoptosis. The sub G1 peak stained by PI was 14.23% at 10-4 mol/L dopamine after culture for 3 days compared with the control (0.81%) in flow cytometry.Conclusion Dopamine inhibites proliferation and induces both differentiation and apoptosis of K562 leukaemia cells.

  12. The effect of scheduling in children undergoing prophylactic cranial irradiation for acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Costello, A.S.; Jones, R.D.; Barrett, A. (Western Infirmary, Glasgow (United Kingdom). Beatson Oncology Centre, Department of Radiation Oncology)

    1991-09-01

    Control of central nervous system disease and overall survival have been analysed in a group of 829 children with leukaemia entered into the UKALL VIII trial to determine whether scheduling of the cranial irradiation is of prognostic significance. It is shown that short gaps in treatment do not influence prognosis and that current radiotherapy practice need not be modified. (author). 20 refs., 1 fig., 2 tabs.

  13. The GIT–PIX complexes regulate the chemotactic response of rat basophilic leukaemia cells

    OpenAIRE

    Gavina, Manuela; Za, Lorena; Molteni, Raffaella; Pardi, Ruggero; Curtis, Ivan de

    2010-01-01

    Background information. Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. The GIT–PIX protein complexes are involved in the regulation of cell motility and adhesion and in the endocytic traffic of members of the family of G-protein-coupled receptors. We have investigated the function of the endogenous GIT complexes in the regulation of cell motility stimulated by fMLP (formyl-Met-Leu-Phe) peptide, in a rat basophilic leukaemia RBL-...

  14. The pharmacokinetics of subcutaneous cytosine arabinoside in patients with acute myelogenous leukaemia.

    OpenAIRE

    Slevin, M L; Piall, E M; Aherne, G.W.; Johnston, A.; Sweatman, M C; Lister, T. A.

    1981-01-01

    1 The pharmacokinetics of subcutaneous cytosine arabinoside were compared with bolus intravenous injection and intravenous infusion in five patients with acute myelogenous leukaemia. 2 Subcutaneous cytosine arabinoside was rapidly absorbed and then declined biexponentially with initial and terminal half-lives similar to intravenous bolus injection. 3 Cytosine arabinoside levels declined rapidly after intravenous bolus and subcutaneous bolus injection, and fell below steady state infusion leve...

  15. Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS)

    International Nuclear Information System (INIS)

    Since July 2015 the study ''ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS) - an international cohort study'' is available. INWORKS comprised data from 300.000 occupational exposed and dosimetric monitored persons from France, USA and UK. The contribution is a critical discussion of this study with respect to the conclusion of a strong evidence of positive associations between protracted low-dose irradiation exposure and leukemia.

  16. Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS)

    Energy Technology Data Exchange (ETDEWEB)

    Lorenz, Bernd

    2015-07-01

    Since July 2015 the study ''ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS) - an international cohort study'' is available. INWORKS comprised data from 300.000 occupational exposed and dosimetric monitored persons from France, USA and UK. The contribution is a critical discussion of this study with respect to the conclusion of a strong evidence of positive associations between protracted low-dose irradiation exposure and leukemia.

  17. PLZF/RARalpha binding partners and their influence on the induction of acute promyelocytic leukaemia

    OpenAIRE

    Frech, Miriam

    2014-01-01

    The acute promyelocytic leukaemia (APL) accounts for 10% of the adult AML patients. APL patients carry chromosomal translocations involving the rarα gene on chromosome 17. The most frequent translocations lead to the expression of the fusion proteins PML/RARα (98%; t(15;17)) and PLZF/RARα (1%; t(11;17)) (X-RARα). The APL is characterised by a differentiation block at the promyelocytic stage and leads to an increased amount of myel...

  18. Transmission of bovine leukaemia virus within dairy herds by simulation modelling

    OpenAIRE

    Monti, G.E.; Frankena, K.; Jong, de, T.

    2007-01-01

    In Argentina, bovine leukaemia virus (BLV) infection is common in dairy herds. The country currently has a National Voluntary Control Programme but relatively few farms have enrolled. However, there is increased interest from authorities and farmers to implement regional compulsory programmes but there is scarce quantitative information of the transmission of BLV in cattle herds. This information is a prerequisite to develop effective BLV control strategies. Mathematical modelling offers ways...

  19. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

    OpenAIRE

    Burger, Jan A.; Landau, Dan A.; Taylor-Weiner, Amaro; Bozic, Ivana; Zhang, Huidan; Sarosiek, Kristopher; Wang, Lili; Stewart, Chip; Fan, Jean; Hoellenriegel, Julia; Sivina, Mariela; Dubuc, Adrian M.; Fraser, Cameron; Han, Yulong; Li, Shuqiang

    2016-01-01

    Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300...

  20. Leukaemia complicating treatment for Hodgkin's disease: the experience of the British National Lymphoma Investigation.

    OpenAIRE

    Devereux, S; Selassie, T G; Vaughan Hudson, G.; Vaughan Hudson, B; Linch, D. C.

    1990-01-01

    OBJECTIVE--To determine the incidence of and risk factors for the development of secondary acute leukaemia and myelodysplasia in patients treated in British National Lymphoma Investigation's studies of Hodgkin's disease since 1970. PATIENTS--2676 Patients entered into Hodgkin's disease studies between February 1970 and November 1986. Data accrued up to November 1988 were analysed, ensuring a minimum follow up period of two years. DESIGN--Retrospective analysis of multicentre trial data by cas...

  1. Combined Bezafibrate and Medroxyprogesterone Acetate: Potential Novel Therapy for Acute Myeloid Leukaemia

    OpenAIRE

    Khanim, Farhat L.; Hayden, Rachel E.; Jane Birtwistle; Alessia Lodi; Stefano Tiziani; Davies, Nicholas J; Ride, Jon P.; Viant, Mark R.; Gunther, Ulrich L.; Mountford, Joanne C; Heinrich Schrewe; Green, Richard M.; Murray, Jim A.; Drayson, Mark T; Chris M Bunce

    2009-01-01

    BACKGROUND: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. PRINCIPAL FINDINGS: Here we demonstrate the potent anti-leukaemic activity of the combination of t...

  2. Acute lymphoblastic leukaemia among Spanish children and mothers' occupation: a case-control study.

    OpenAIRE

    Infante-Rivard, C; Mur, P.; Armstrong, B; ALVAREZ-DARDET, C.; Bolumar, F

    1991-01-01

    STUDY OBJECTIVE: The aim was to investigate the association between mothers' occupational exposure during pregnancy and the incidence of acute lymphoblastic leukaemia in children. DESIGN: The study was a case-control investigation. A face to face interview was used to assess exposures at work and relevant confounding variables. SETTING: The study was community based and was carried out in five provinces of Spain. SUBJECTS: 128 cases less than 15 years of age were interviewed (91% of those eli...

  3. Development of Drugs Targeting the PI3K Signalling Pathway in Leukaemias and Lymphomas

    Directory of Open Access Journals (Sweden)

    Alexandre Arcaro

    2015-03-01

    Full Text Available The phosphoinositide 3-kinase (PI3K family of signalling enzymes play a key role in the transduction of signals from activated cell surface receptors controlling cell growth and proliferation, survival, metabolism, and migration. The intracellular signalling pathway from activated receptors to PI3K and its downstream targets v-akt murine thymoma viral oncogene homolog (Akt and mechanistic target of rapamycin (mTOR is very frequently deregulated by genetic and epigenetic mechanisms in human cancer, including leukaemia and lymphoma. In the past decade, an arsenal of small molecule inhibitors of key enzymes in this pathway has been developed and evaluated in pre-clinical studies and clinical trials in cancer patients. These include pharmacological inhibitors of Akt, mTOR, and PI3K, some of which are approved for the treatment of leukaemia and lymphoma. The PI3K family comprises eight different catalytic isoforms in humans, which have been subdivided into three classes. Class I PI3K isoforms have been extensively studied in the context of human cancer, and the isoforms p110α and p110δ are validated drug targets. The recent approval of a p110δ-specific PI3K inhibitor (idelalisib/Zydelig® for the treatment of selected B cell malignancies represents the first success in developing these molecules into anti-cancer drugs. In addition to PI3K inhibitors, mTOR inhibitors are intensively studied in leukaemia and lymphoma, and temsirolimus (Torisel® is approved for the treatment of a type of lymphoma. Based on these promising results it is hoped that additional novel PI3K pathway inhibitors will in the near future be further developed into new drugs for leukaemia and lymphoma.

  4. Cognitive outcome in children and adolescents treated for acute lymphoblastic leukaemia with chemotherapy only

    OpenAIRE

    Lofstad, G Elisabeth; Reinfjell, Trude; Hestad, Knut; Diseth, Trond H

    2009-01-01

    Objective: To examine cognitive outcome in children and adolescents with acute lymphoblastic leukaemia (ALL) in remission, treated with central nervous system prophylactic chemotherapy only. Method: Thirty-five children and adolescents, age 8.4–15.3 years in long-term remission from ALL, 4.2–12.4 years post diagnosis, without relapse and no prediagnosis history of neurodevelopmental disorder were compared with 35 healthy controls matched for gender and age, on measures of intellectual functio...

  5. Early molecular diagnosis of aspergillosis in a patient with acute myeloid leukaemia

    OpenAIRE

    Greco, R; Mancini, N.; Peccatori, J.; Cieri, N.; Vago, L.; F. Giglio; Morelli, M; Ghidoli, N; Carletti, S; Levati, G; Crucitti, L; E. Sala; Lupo Stanghellini, M T; Lorentino, F; Forcina, A

    2014-01-01

    Diagnosis of invasive fungal infection remains challenging. Here we report a case of early diagnosis of invasive aspergillosis in a neutropenic patient affected by acute myeloid leukaemia, achieved through the detection of Aspergillus fumigatus species-specific ribonucleic acid sequences by a sensitive multiplex real-time polymerase chain reaction-based molecular assay. Thanks to the early diagnosis, targeted therapy was promptly established and the severe fungal infection controlled, allowin...

  6. The 1957 MRC report on leukaemia and aplastic anaemia in patients irradiated for ankylosing spondylitis

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Peter G [London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT (United Kingdom)

    2007-12-15

    The estimation of the carcinogenic effects of exposure to low doses of ionizing radiation has depended primarily on extrapolation from effects seen in two populations exposed to relatively high doses-the survivors of the atomic bomb explosions in Japan and patients treated in the UK with x-rays for the arthritic condition ankylosing spondylitis. The study of the leukaemia risk in over 14000 irradiated spondylitis patients was completed in an astonishingly short period of time in the mid-1950s. The full report of the original study has been difficult to access because it was not published in a journal but only as a Special Report of the UK Medical Research Council. To mark 50 years since this publication this full report is reproduced in this issue of the Journal. This accompanying review describes the background to the study, the principal findings and the further follow-up of the population that documented the risks of cancers in addition to leukaemia associated with the x-ray treatment. The architects of the study were a radiobiologist, Michael Court-Brown, and an epidemiologist, Richard Doll. Their very productive study of the leukaemia risk among spondylitics spawned a lifelong collaboration including further seminal studies of the carcinogenic effects of radiation exposure, which are also summarised in the review. (review)

  7. Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia HL-60 Cells.

    Science.gov (United States)

    Bejarano, Ignacio; Godoy-Cancho, Belén; Franco, Lourdes; Martínez-Cañas, Manuel A; Tormo, María A

    2015-08-01

    Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro-apoptotic events in cancerous cells. However, the literature related to the anti-cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase-3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time-dependent and dose-dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase-3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti-cancer properties. Moreover, it opens new possibilities of application of cork by-products, being more efficient in the sector of cork-based agriculture. Copyright © 2015 John Wiley & Sons, Ltd.

  8. BRAF mutation detection in hairy cell leukaemia from archival haematolymphoid specimens.

    Science.gov (United States)

    Thomas, Carla; Amanuel, Benhur; Finlayson, Jill; Grieu-Iacopetta, Fabienne; Spagnolo, Dominic V; Erber, Wendy N

    2015-06-01

    Hairy cell leukaemia (HCL) is a rare, indolent chronic B-cell leukaemia accounting for approximately 2% of all adult leukaemias. The recent association of the BRAF p.Val600Glu (V600E) mutation in HCL makes it a valuable molecular diagnostic marker. We compared the ability of Sanger sequencing, fluorescent single-strand conformational polymorphism (F-SSCP) and high resolution melting (HRM) analysis to detect BRAF mutations in 20 cases of HCL consisting of four archival Romanowsky stained air-dried peripheral blood and bone marrow aspirate smears, 12 mercury fixed decalcified bone marrow trephine biopsies, three formalin fixed, paraffin embedded (FFPE) splenectomy samples and one fresh peripheral blood sample. DNA was amplified and BRAF mutation status determined by the three methods above. V600E mutation was identified in 94%, 89% and 72% of HCL cases by F-SSCP, HRM and Sanger sequencing, respectively. In one case, in addition to the p.Val600Glu mutation, a p.Lys601Thr (K601T) mutation was identified. DNA from archival slide scrapings, mercury-fixed and FFPE tissue can be used to identify BRAF mutations with high sensitivity, especially using HRM/F-SSCP. The V600E mutation can be used as a supplementary molecular marker to aid in the diagnosis of HCL and the presence of the mutation may provide a target for therapy. PMID:25938346

  9. Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia.

    Directory of Open Access Journals (Sweden)

    Amanda Dixon-McIver

    Full Text Available Acute myeloid leukaemia (AML is the most common acute leukaemia in adults; however, the genetic aetiology of the disease is not yet fully understood. A quantitative expression profile analysis of 157 mature miRNAs was performed on 100 AML patients representing the spectrum of known karyotypes common in AML. The principle observation reported here is that AMLs bearing a t(15;17 translocation had a distinctive signature throughout the whole set of genes, including the up regulation of a subset of miRNAs located in the human 14q32 imprinted domain. The set included miR-127, miR-154, miR-154*, miR-299, miR-323, miR-368, and miR-370. Furthermore, specific subsets of miRNAs were identified that provided molecular signatures characteristic of the major translocation-mediated gene fusion events in AML. Analysis of variance showed the significant deregulation of 33 miRNAs across the leukaemic set with respect to bone marrow from healthy donors. Fluorescent in situ hybridisation analysis using miRNA-specific locked nucleic acid (LNA probes on cryopreserved patient cells confirmed the results obtained by real-time PCR. This study, conducted on about a fifth of the miRNAs currently reported in the Sanger database (microrna.sanger.ac.uk, demonstrates the potential for using miRNA expression to sub-classify cancer and suggests a role in the aetiology of leukaemia.

  10. The 1957 MRC report on leukaemia and aplastic anaemia in patients irradiated for ankylosing spondylitis

    International Nuclear Information System (INIS)

    The estimation of the carcinogenic effects of exposure to low doses of ionizing radiation has depended primarily on extrapolation from effects seen in two populations exposed to relatively high doses-the survivors of the atomic bomb explosions in Japan and patients treated in the UK with x-rays for the arthritic condition ankylosing spondylitis. The study of the leukaemia risk in over 14000 irradiated spondylitis patients was completed in an astonishingly short period of time in the mid-1950s. The full report of the original study has been difficult to access because it was not published in a journal but only as a Special Report of the UK Medical Research Council. To mark 50 years since this publication this full report is reproduced in this issue of the Journal. This accompanying review describes the background to the study, the principal findings and the further follow-up of the population that documented the risks of cancers in addition to leukaemia associated with the x-ray treatment. The architects of the study were a radiobiologist, Michael Court-Brown, and an epidemiologist, Richard Doll. Their very productive study of the leukaemia risk among spondylitics spawned a lifelong collaboration including further seminal studies of the carcinogenic effects of radiation exposure, which are also summarised in the review. (review)

  11. Breaking bad news--parents' experience of learning that their child has leukaemia.

    LENUS (Irish Health Repository)

    Oshea, J

    2012-02-03

    This study aimed to seek parents\\' experiences of how they learned their child had leukaemia and therefore identify ways of improving this process. To achieve this task a questionnaire was designed to ask parents about specific elements of the initial interview and give them opportunity to add their thoughts and feelings on the subject. All children with a diagnosis of leukaemia over an eighteen-year period were identified and parents of those children still alive were invited to partake in the study. 49 out of 50 families agreed to participate of which 35 (72%) returned completed questionnaires. The majority 29 (83%) expressed overall satisfaction. Their replies confirmed some findings of previous studies, and also offered some new insights. Examples of new findings or expansion on previous findings include observations on the presence of young children at the initial interview; the importance of the language used in conveying the diagnosis and prognostic information, and a preference for actuarial terms when discussing prognosis. Telling parents their child has leukaemia is a challenging and important task. The experience of parents gives us valuable insights into our own communication skills and highlights areas of possible improvement in this difficult area.

  12. Childhood trauma and childhood urbanicity in relation to psychotic disorder

    NARCIS (Netherlands)

    Frissen, Aleida; Lieverse, Ritsaert; Drukker, Marjan; van Winkel, Ruud; Delespaul, Philippe; Cahn, W

    2015-01-01

    BACKGROUND: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect

  13. Childhood as a value

    OpenAIRE

    EWELINA PIECUCH

    2011-01-01

    The article encompasses the problems of childhood and its influence on the rest of one's life. I have concentrated on this crucial and specific time in life. It is demonstrated by biology, medicine, psychology, and psychoanalysis that human habits are formed in childhood. Health, hygiene and aesthetic behaviour determine one's further fate and influence life in its entirety. It is that phase of human life that determines the rest of it. In childhood children manifest their cogn...

  14. Medical Research Council leukaemia trial--UKALL V: an attempt to reduce the immunosuppressive effects of therapy in childhood acute lymphoblastic leukemia. Report to the Council by the Working Party on Leukaemia in Childhood.

    Science.gov (United States)

    Chessells, J M; Durrant, J; Hardy, R M; Richards, S

    1986-12-01

    The Medical Research Council UKALL V trial for children with standard-risk acute lymphoblastic leukemia (ALL) (aged 1 to 14 years, leucocyte count less than 20 X 10(9)/L) was designed to determine whether the immunosuppressive effects of treatment could be reduced without sacrifice of antileukemic effect by alterations in the type of continuing therapy or in fractionation of cranial irradiation. Remission was achieved in 496 children on standard induction therapy, and 309 children received 24 Gy of cranial irradiation in ten to 16 fractions over 21 days, and 174 received 21 Gy in five to nine fractions over 21 days. The type of radiotherapy administered had no influence on relapse at any site or rate of death in remission. All 496 children were randomized to receive chemotherapy for 2 or 3 years with 6-mercaptopurine and methotrexate either as a continuous (group C) or a semicontinuous (group G) regimen or as a five-day pulse every 3 weeks (group I). All groups also received vincristine and prednisolone every 6 weeks. With a minimum follow-up of almost 7 years, patients in group I had significantly fewer remission deaths (P = .025) but a much higher rate of bone marrow relapse than those in group C or G (P = .002). There was an overall benefit for 3 years of chemotherapy compared with 2 years, which in contrast to previous studies, was more apparent in girls and in patients in groups C and G. Testicular relapse occurred in 37 boys, including 19 patients off therapy, with a previously negative biopsy. The overall results confirmed the prognostic significance of initial leucocyte count, even among these standard-risk patients, while girls had a superior rate of disease-free survival, but not of hematologic remission. It is concluded that, even among standard-risk patients, the prognosis is influenced by the height of the initial leukocyte count. While alterations in the fractionation of cranial irradiation do not appear to have influenced disease-free survival, intermittent continuing chemotherapy, although less immunosuppressive, is less effective than conventional continuous therapy in the treatment of ALL. In this study, 3 years of chemotherapy appeared superior to 2 years. PMID:3537216

  15. Evidence that continued remission in patients treated for acute leukaemia is dependent upon autologous natural killer cells.

    Science.gov (United States)

    Lowdell, Mark W; Craston, Rose; Samuel, David; Wood, Marion E; O'Neill, Elena; Saha, Vaskar; Prentice, H Grant

    2002-06-01

    Although it has been known for more than 40 years that allogeneic immune responses cure leukaemias after bone marrow transplantation, autologous leukaemia-specific immunity remains controversial and its impact upon survival has not been established. Here we have tested 25 patients with de novo acute leukaemias, while in remission at completion of their anti-leukaemia therapy, for evidence of autologous cytolytic immunity to their leukaemic cells taken and cryopreserved at disease presentation. We have measured this degree of cell-mediated cytotoxicity in vitro and termed it "leukaemia cytolytic activity" (LCA). Patients whose disease ultimately relapsed had significantly lower LCA than those who remained in remission beyond 2 years (P LCA when in remission predicted subsequent relapse within 2 years with a sensitivity of 100% and specificity of 77%. LCA was mediated in vitro by CD56+/CD8alpha+/CD3- natural killer cells. We propose that it is this immune response, rather than the chemotherapy per se, which is responsible for continued remission and that measurement of LCA in patients at completion of therapy may be used as an indicator of risk of subsequent relapse. Patients lacking this response will require further treatment, either with an allogeneic donor transplant or an alternative immunotherapeutic strategy. PMID:12060116

  16. ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling

    NARCIS (Netherlands)

    S. Goossens (Steven); E. Radaelli (Enrico); O. Blanchet (Odile); K. Durinck (Kaat); J. van der Meulen (Joni); S. Peirs (Sofie); T. Taghon (Tom); C.S. Tremblay (Cedric S.); M. Costa (Magdaline); M.F. Ghahremani; J. De Medts (Jelle); S. Bartunkova (Sonia); K. Haigh (Katharina); C. Schwab (Claire); N. Farla (Natalie); T. Pieters (Tim); F. Matthijssens (Filip); N. van Roy (Nadine); J.A. Best (J. Adam); K. Deswarte (Kim); P. Bogaert (Pieter); C. Carmichael (Catherine); A. Rickard (Adam); S. Suryani (Santi); L.S. Bracken (Lauryn S.); R. Alserihi (Raed); K. Canté-Barrett (Kirsten); L. Haenebalcke (Lieven); E. Clappier; P. Rondou (Pieter); K. Slowicka (Karolina); D. Huylebroeck (Danny); A.W. Goldrath (Ananda W.); V. Janzen (Viktor); M.P. McCormack (Matthew P.); R.B. Lock (Richard B.); D.J. Curtis (David J.); C.J. Harrison (Christine); G. Berx (Geert); F. Speleman (Franki); J.P.P. Meijerink (Jules); J. Soulier (Jean); P. van Vlierberghe (Pieter); K. Haigh (Katharina)

    2015-01-01

    textabstractEarly T-cell precursor leukaemia (ETP-ALL) is a high-risk subtype of human leukaemia that is poorly understood at the molecular level. Here we report translocations targeting the zinc finger E-box-binding transcription factor ZEB2 as a recurrent genetic lesion in immature/ETP-ALL. Using

  17. Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique.

    NARCIS (Netherlands)

    Balgobind, B.V.; Hollink, I.H.; Reinhardt, D.; Wering, E.R. van; Graaf, S.S.N. de; Baruchel, A.; Stary, J.; Beverloo, H.B.; Greef, G.E. de; Pieters, R.; Zwaan, C.M.; Heuvel-Eibrink, M.M. van den

    2010-01-01

    Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies i

  18. Childhood Cancer Survivor Study: An Overview

    Science.gov (United States)

    ... Cancers of Childhood Treatment Childhood Cancer Genomics Research Childhood Cancer Survivor Study: An Overview In 2016, it ... Late Effects of Treatment for Childhood Cancer .) The Childhood Cancer Survivor Study ( CCSS ), funded by the National ...

  19. EDRP public local inquiry, UKAEA/BNFL precognition on: Concern about childhood leukaemia in the West of Scotland

    International Nuclear Information System (INIS)

    Date relating to the West of Scotland Cancer Registry Region, comprising 26 local government districts and containing 4 nuclear installations, are presented. The data relate to children aged 0-14 years. (UK)

  20. Genome‐wide analysis of cytogenetic aberrations in ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wesolowska, Agata; Joshi, Tejal;

    2012-01-01

    , and gains of 10 and 21) seemed independent of each other. Finally, we identified the most common regions with recurrent gains and losses, which comprise microRNA clusters with known oncogenic or tumour‐suppressive roles. The present study sheds further light on the genetic diversity of ETV6/RUNX1‐positive...

  1. A review of epidemiological studies concerning leukaemia and lymphoma among young people and the genetic effects of ionizing radiation

    International Nuclear Information System (INIS)

    The review seeks to identify consistent patterns of results between 30 epidemiological studies of low dose parental exposure to radiation and leukaemia etc. in their offspring. Eight of the studies show significant increases in leukaemia but most are unreliable because they have flawed methodologies and several analyse the same basic data. Two studies free from major criticism do show an association with parental irradiation but both contain data from Seascale and are not independent. Two well conducted studies based on other areas (Canada and Scotland) are claimed by their authors to have sufficient statistical power to test the Seascale findings and do not confirm an association with paternal irradiation. It is concluded that there is little reliable evidence from epidemiological studies for a causal association between pre-conception, paternal or maternal, irradiation and an increase in the frequency of leukaemia or malignancies among offspring. (author)

  2. Child leukaemia and low frequency electromagnetic fields; Les leucemies de l'enfant et les champs electromagnetiques basse frequence

    Energy Technology Data Exchange (ETDEWEB)

    Clavel, J.

    2009-07-01

    The author discusses the possible causes of child leukaemia: exposure to natural ionizing radiation (notably radon), to pesticides, and to hydrocarbons emitted by road traffic. Some studies suggested that an inadequate reaction of the immune system to an ordinary infection could result in leukaemia. Other factors are suspected, notably extremely low frequency electromagnetic fields, the influence of which is then discussed by the author. She evokes and discusses results of different investigations on this topic which have been published since the end of the 1970's. It appears that a distance less than 50 meters from high voltage lines or the vicinity of transformation stations may double the risk of child leukaemia

  3. Childhood Obesity. ERIC Digest.

    Science.gov (United States)

    Summerfield, Liane M.

    In this discussion of childhood obesity, the medical and psychological problems associated with the condition are noted. Childhood obesity most likely results from an interaction of nutritional, psychological, familial, and physiological factors. Three factors--the family, low-energy expenditure, and heredity--are briefly examined. Early…

  4. Adult acute lymphoblastic leukaemia in Denmark. A national population-based retrospective study on acute lymphoblastic leukaemia in Denmark 1998-2008

    DEFF Research Database (Denmark)

    Toft, Nina; Schmiegelow, Kjeld; Klausen, Tobias W;

    2012-01-01

    Since July 2008, children and adults 1-45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared with...... intended treatment, the pEFS(5y) and pOS(5y) were 36·6% and 44·1%, respectively, with a significantly higher pOS(5y) for patients 15-35 years compared with patients 36-65 years (50·7% vs. 38·9%, P = 0·006). Cox multiple regression analysis identified age (Hazard Ratio = 1·7, P ...

  5. Paternal preconceptional radiation exposure in the nuclear industry and leukaemia and non-Hodgkin's lymphoma in young people in Scotland.

    OpenAIRE

    Kinlen, L. J.; Clarke, K; Balkwill, A

    1993-01-01

    OBJECTIVE--To determine if a relation exists between paternal exposure to relatively high levels of radiation in the Scottish nuclear industry and the risk of leukaemia and non-Hodgkin's lymphoma is subsequently conceived children. DESIGN--Matched case-control study with three controls for each case. SETTING--The whole of Scotland. SUBJECTS--The fathers of 1024 children with leukaemia and 237 children with non-Hodgkin's lymphoma diagnosed in Scotland below the age of 25 among those born in Sc...

  6. Evolution of resistance to Aurora kinase B inhibitors in leukaemia cells.

    Directory of Open Access Journals (Sweden)

    Timothy W Failes

    Full Text Available Aurora kinase inhibitors are new mitosis-targeting drugs currently in clinical trials for the treatment of haematological and solid malignancies. However, knowledge of the molecular factors that influence sensitivity and resistance remains limited. Herein, we developed and characterised an in vitro leukaemia model of resistance to the Aurora B inhibitor ZM447439. Human T-cell acute lymphoblastic leukaemia cells, CCRF-CEM, were selected for resistance in 4 µM ZM447439. CEM/AKB4 cells showed no cross-resistance to tubulin-targeted and DNA-damaging agents, but were hypersensitive to an Aurora kinase A inhibitor. Sequencing revealed a mutation in the Aurora B kinase domain corresponding to a G160E amino acid substitution. Molecular modelling of drug binding in Aurora B containing this mutation suggested that resistance is mediated by the glutamate substitution preventing formation of an active drug-binding motif. Progression of resistance in the more highly selected CEM/AKB8 and CEM/AKB16 cells, derived sequentially from CEM/AKB4 in 8 and 16 µM ZM447439 respectively, was mediated by additional defects. These defects were independent of Aurora B and multi-drug resistance pathways and are associated with reduced apoptosis mostly likely due to reduced inhibition of the catalytic activity of aurora kinase B in the presence of drug. Our findings are important in the context of the use of these new targeted agents in treatment regimes against leukaemia and suggest resistance to therapy may arise through multiple independent mechanisms.

  7. Abscopal induction of leukaemia and osteosarcoma following administration of alpha-emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Lord, B.I. (Paterson Institute for Cancer Research, Christie Hospital Manchester, Manchester (United Kingdom))

    2008-12-15

    Alpha-particle-emitting, bone-seeking radionuclides can induce leukaemia and/ or osteosarcoma in mice. Furthermore, plutonium-239, given to male mice before mating with normal females, while not directly leading to leukaemia in the progeny does lead to enhanced susceptibility to leukaemogenic agents. In the first case, the amounts of radionuclide are very small in experimental terms; and zero in the case of transgenerational activity. In both cases, the development of the disorders is remote in time and location relative to that of the contaminating radionuclide, making interpretation of the mechanisms and estimation of radiation risk problematic. It is necessary, then, to address questions involving the basis of haemopoiesis itself. Cellular kinetics of the development of blood from the pluripotent stem cells to the mature functional cells are outlined, describing compensatory proliferation mechanisms and extensive movement of cells throughout the marrow space. The locations of potential oncogenic target cells are identified and the nature of the stromal microenvironment that regulates haemopoiesis is defined. Plutonium-239, given to male mice, targets spermatogenesis at the stem cell level leaving unidentified damage that is inherited by his offspring. This leaves the offspring susceptible to a leukaemogenic agent encountered later in life. The characteristics of this, corroborated by consideration of the cellular kinetics, are of an inherited genomic instability. Cells of the microenvronment, inheriting the same genetic damage, probably act in the role of an enhancing 'bystander'. In adult mice, the mechanisms are different. Bone turnover results in radioactivity being gradually transported through the marrow by long-lived macrophages. A model based on temporal microdistributions of activity, defining specific target cell regions, is able to illustrate that considering bone marrow as a uniform mass of cells is inadequate to describe the observed

  8. PCR-based clonality assessment in patients with lymphocytic leukaemias: a single-institution experience

    Indian Academy of Sciences (India)

    Bojana M. Cikota; Ljiljana J. Tukić; Olivera T. Tarabar; Dragana T. Stamatović; Marija N. Elez; Zvonko M. Magić

    2009-12-01

    PCR-based clonality testing can be performed in all lymphoproliferations by analysing gene rearrangements of antigen receptors, rearrangements that are unique for each kind of lymphocyte. Reactive lymphoproliferations have polyclonally rearranged Ig/TCR genes, whereas malignant proliferations (leukaemias and lymphomas) show clonal rearrangements. The aim of this study was to assess the clinical benefits of clonality testing with previously evaluated consensus primers in leukaemia patients. The study included peripheral blood and bone marrow samples of 67 leukaemia patients (32 B-CLL, 24 B-ALL and 11 T-ALL). Clonality testing was based on PCR amplification of rearranged I$_{\\text{gH}}$ and TCR genes. During diagnosis, monoclonal pattern was found in all analysed B-CLL and T-ALL samples. Testing in B-ALL patients showed positive results in all bone marrow and one peripheral blood samples. Results of clonality testing in B-CLL patients during follow-up were concordant between peripheral blood and bone marrow. Obtained results corresponded to clinical course in all but one patient. In B-ALL group, results of molecular testing in peripheral blood and bone marrow confirmed remission estimated according to clinical criteria in all except one patient. Before any clinical sign of relapse, monoclonal pattern was found in six/seven patients by bone marrow and in three/seven patients by peripheral blood analysis, respectively. Results of molecular monitoring in T-ALL patients did not confirme clinical evaluation in two patients. Obtained results indicate high accuracy of re-evaluated primers for clonality assessment in ALL and CLL patients at the time of diagnosis. Results of clonality testing in B-ALL patients indicate that bone marrow analysis has higher sensitivity compared to analysis of peripheral blood.

  9. [Dasatinib. A novel tyrosine kinase inhibitor for the treatment of chronic myeloid leukaemia

    DEFF Research Database (Denmark)

    Dufva, I.H.; Stentoft, J.; Hasselbalch, H.C.;

    2008-01-01

    Chronic myeloid leukaemia is characterized by an abnormal tyrosin kinase in the cytoplasm of the clonal cells. The enzyme is derived from a fusion gene on the Philadelphia-chromosome, evolved by a translocation between chromosomes 9 and 22. Understanding the biology of the tyrosin kinase led to t...... targeted therapy, inhibiting the ATP-binding site by a small molecule--imatinib (Glivec). A novel 2nd generation tyrosin kinase inhibitor--dasatinib (Sprycel)--is now available in cases of insufficient response or intolerance to imatinib Udgivelsesdato: 2008/1/28...

  10. A Clinicopathological Correlation of Acute Leukaemias in relation to Immunophenotyping and Cytogenetics

    Directory of Open Access Journals (Sweden)

    Sunil Pazhayanur Venkateswaran

    2012-10-01

    Full Text Available Introduction: Leukemia accounts for 0.15 – 0.6% of the total medical admissions in many general hospitals in India. Frequency of leukemia seen in India of Acute Myeloid leukaemia (AML is 20 - 25% and Acute Lymphoblastic leukaemia (ALL is 15-25%. The Annual incidence rate of AML and ALL are 5.6 and 30.9 per million population respectively. Aims: To study the clinicopathological correlation in Acute myeloid and Acute Lymphoblastic leukaemias in relation to immunophenotyping and cytogenetics. Materials & Methods: All newly diagnosed cases of acute myeloid leukaemia that presented to our hospital from January 2007 to July 2009 were included in this study. The peripheral blood and bone marrow were tested for surface membrane, cytoplasmic and nuclear antigens and were classified by the French-American- British (FAB Cooperative Group Classification by using Romanowsky (Leishman and May Grunwald Giemsa[MGG] stained smears and cytochemical stains. Results & Summary: A series of available 100 cases of Acute Leukemia diagnosed during a period of 30 months (January 2007 to July 2009 were reviewed and various clinical, biochemical, immunophenotypic and cytogenetic parameters were assessed. 88 cases were subject to immunophenotyping and 60 cases were subject to cytogenetic analysis either by conventional Karyotyping, FISH (fluorescence in situ hybridization and RT-PCR (Reverse transcriptase polymerase chain reaction. The antigen expressions by immunophenotype in acute myeloid and lymphoblastic leukemias were compared with age, Haemoglobin, Total WBC count, Platelet counts, Lactate dehydrogenase levels and abnormal karyotypes. Analytical statistics showed a significant correlation in the expressions of CD13, CD33, CD117 and CD64 in Acute Myeloid Leukemia and CD10, CD19, CD20 and CD22 in Acute Lymphoblastic leukemia and the expressions of CD13/CD117, CD3/CD10/CD22,CD3/CD5/CD2 and CD117/CD11c were related to the age, Haemoglobin, WBC count and Lactate

  11. Visuomotor function in children treated for acute lymphoblastic leukaemia with chemotherapy only.

    Science.gov (United States)

    Knight, Sarah; McCarthy, Maria; Anderson, Vicki; Hutchinson, Esther; De Luca, Cinzia

    2014-01-01

    This study aimed to evaluate visuomotor function in children treated for acute lymphoblastic leukaemia (ALL). The performance of 64 children, 1-7 years post-chemotherapy for ALL, was compared to that of their healthy peers (n = 56) on visuomotor integration (VMI) and motor coordination (MC) tasks. Children posttreatment for ALL displayed significantly reduced VMI, but not MC, performances as compared to controls. Children treated on chemotherapy-only ALL regimes are at heightened risk for visuomotor integration deficits. Monitoring of visuomotor skills and implementation of appropriate interventions targeting higher level visuomotor integration skills should form an important component of any ALL long-term effects program. PMID:24571929

  12. Human retroviruses in leukaemia and AIDS: reflections on their discovery, biology and epidemiology.

    Science.gov (United States)

    Karpas, Abraham

    2004-11-01

    The study of retroviruses has had a profound impact by unveiling an unusual form of viral replication: the multiplication of RNA viruses via a proviral DNA, for which Jan Svoboda provided the experimental model over forty years ago. In 1970 Temin, Mizutani and Baltimore discovered that this group of viruses contains a unique enzyme catalysing the synthesis of a DNA copy of the viral RNA: reverse transcriptase (RT). The discovery of RT has itself had an enormous impact on molecular biology in general, but also stimulated many premature claims of its detection in human disease. Claims by Gallo's laboratory that the cytoplasm of human leukaemia cells contained RT proved to be unfounded, as did his report in collaboration with Weiss that myeloid leukaemia contained HL23 virus, this organism proving not to be human but a laboratory contaminant of three monkey viruses. Conclusive demonstration of a retroviral involvement in human leukaemia was first provided in 1981 by Hinuma and his associates, showing that adult T-cell leukaemia (ATL), a rare form of leukaemia endemic to south-west Japan, is caused by a new retrovirus (ATLV). Other publications in December 1980 and through 1981 claimed the discovery of a new human T-cell leukaemia virus involved in mycosis fungoides (MF) and Sézary's syndrome (SS). This virus was termed HTLV by Gallo. The nucleotide sequence of ATLV is strongly conserved, that of my 1983 isolate from a black British ATL patient being practically identical with the Japanese virus isolates. After AIDS was recognised in 1981 by Gottlieb and coworkers as a new human disease, several papers were published by Gallo and his associates during 1983-4, invoking the oncovirus responsible for adult T-cell leukaemia as the cause of AIDS. In 1983 the French scientist Barré-Sinoussi and her colleagues succeeded in isolating a new agent in the disease, a lentivirus, which they named LAV. The French immunologist Klatzmann and his colleagues discovered that LAV killed

  13. Immunological and molecular biological identification of a true case of T-hairy cell leukaemia

    DEFF Research Database (Denmark)

    Demeter, J; Pálóczi, K; Földi, J;

    1990-01-01

    A hairy cell leukaemia (HCL) patient is presented in whom the peripheral blood mononuclear cells (PBMCs) carried suppressor T-cell markers (CD3+, CD2+, CD8+/CD4-, CD38+). Analysis of genomic DNA of PBMNC showed the presence of a monoclonal population of T cells, the T-cell receptor (TCR) beta-cha...... RAB-1/CD-8 in a double marker assay. Natural killer activity of PBMNCs against K562 target cells was severely reduced, while the cells were found to exert strong antibody-dependent cellular cytotoxicity. Udgivelsesdato: 1989-Oct...

  14. Inter-species chimeras of leukaemia inhibitory factor define a major human receptor-binding determinant.

    OpenAIRE

    Owczarek, C M; Layton, M. J.; Metcalf, D; Lock, P; Willson, T A; Gough, N M; Nicola, N A

    1993-01-01

    Human leukaemia inhibitory factor (hLIF) binds to both human and mouse LIF receptors (LIF-R), while mouse LIF (mLIF) binds only to mouse LIF-R. Moreover, hLIF binds with higher affinity to the mLIF-R than does mLIF. In order to define the regions of the hLIF molecule responsible for species-specific interaction with the hLIF-R and for the unusual high-affinity binding to the mLIF-R, a series of 15 mouse/human LIF hybrids has been generated. Perhaps surprisingly, both of these properties mappe...

  15. Childhood trauma and childhood urbanicity in relation to psychotic disorder

    OpenAIRE

    Frissen, Aleida; Lieverse, Ritsaert; Drukker, Marjan; van Winkel, Ruud; Delespaul, Philippe; [...

    2015-01-01

    Background Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of childhood trauma increases. Also, any impact of the urban environment on likelihood of exposure to childhood trauma could be stronger in children who later develop psychotic disorder. The aim of...

  16. Childhood trauma and childhood urbanicity in relation to psychotic disorder

    OpenAIRE

    Frissen, Aleida; Lieverse, Ritsaert; Drukker, Marjan; van Winkel, Ruud; Delespaul, Philippe; Cahn, W.

    2015-01-01

    BACKGROUND: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of childhood trauma increases. Also, any impact of the urban environment on likelihood of exposure to childhood trauma could be stronger in children who later develop psychotic disorder. The aim o...

  17. Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia

    Directory of Open Access Journals (Sweden)

    Philipp Koehler

    2012-01-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL remains an incurable disease due to the high risk of relapse, even after complete remission, raising the need to control and eliminate residual tumor cells in long term. Adoptive T cell therapy with genetically engineered specificity is thought to fulfil expectations, and clinical trials for the treatment of CLL are initiated. Cytolytic T cells from patients are redirected towards CLL cells by ex vivo engineering with a chimeric antigen receptor (CAR which binds to CD19 on CLL cells through an antibody-derived domain and triggers T cell activation through CD3ζ upon tumor cell engagement. Redirected T cells thereby target CLL cells in an MHC-unrestricted fashion, secret proinflammatory cytokines, and eliminate CD19+ leukaemia cells with high efficiency. Cytolysis of autologous CLL cells by patient's engineered T cells is effective, however, accompanied by lasting elimination of healthy CD19+ B-cells. In this paper we discuss the potential of the strategy in the treatment of CLL, the currently ongoing trials, and the future challenges in the adoptive therapy with CAR-engineered T cells.

  18. A multicentre trial of live attenuated varicella vaccine in children with leukaemia in remission.

    Science.gov (United States)

    Gershon, A A; Steinberg, S; Gelb, L; Galasso, G; Borkowsky, W; LaRussa, P; Ferrara, A

    1985-01-01

    Two hundred forty children with acute leukaemia in remission for at least 1 year were immunized with live attenuated varicella vaccine. All were susceptible to varicella before immunization. There was a seroconversion to varicella-zoster virus in approximately 85% after 1 dose, and in 97% after 2 doses. The major side effect was mild to moderate rash, seen mainly in children with maintenance chemotherapy suspended for 1 week before and 1 week after vaccination. Vaccinees with rash were at some risk (10%) to transmit vaccine virus to varicella susceptibles with whom they had close contact. Twenty-nine vaccinees were subsequently exposed to varicella in their households. The attack rate of clinical varicella in these vaccinees was 21%, which is significantly lower than the 80%-90% attack rate occurring in varicella susceptibles after household exposure. All these breakthrough cases of varicella were mild, even in leukaemics receiving chemotherapy. Varicella vaccine was approximately 80% effective in preventing clinical varicella in children with leukaemia and completely effective in preventing severe varicella in this high-risk group.

  19. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Cowan-Jacob, Sandra W., E-mail: sandra.jacob@novartis.com; Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W. [Novartis Institutes for Biomedical Research, Basel (Switzerland)

    2007-01-01

    A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia. Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery.

  20. Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, M.; Korogi, Y.; Shigematsu, Y.; Liang, L.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Matsuoka, M. [Second Division of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Yamamoto, T. [Department of Pathology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Jhono, M. [Department of Dermatology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Eto, K. [The National Institute for Minamata Disease, Minamata (Japan)

    2002-07-01

    Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

  1. Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer?

    Directory of Open Access Journals (Sweden)

    Carolyn S. Grove

    2014-08-01

    Full Text Available Acute myeloid leukaemia (AML is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have revealed the spectrum of somatic mutations that give rise to human AML and drawn our attention to its molecular evolution and clonal architecture. It is now evident that most AML genomes harbour small numbers of mutations, which are acquired in a stepwise manner. This characteristic, combined with our ability to identify mutations in individual leukaemic cells and our detailed understanding of normal human and murine haematopoiesis, makes AML an excellent model for understanding the principles of cancer evolution. Furthermore, a better understanding of how AML evolves can help us devise strategies to improve the therapy and prognosis of AML patients. Here, we draw from recent advances in genomics, clinical studies and experimental models to describe the current knowledge of the clonal evolution of AML and its implications for the biology and treatment of leukaemias and other cancers.

  2. Genome-wide analysis of transcriptional reprogramming in mouse models of acute myeloid leukaemia.

    Directory of Open Access Journals (Sweden)

    Nicolas Bonadies

    Full Text Available Acute leukaemias are commonly caused by mutations that corrupt the transcriptional circuitry of haematopoietic stem/progenitor cells. However, the mechanisms underlying large-scale transcriptional reprogramming remain largely unknown. Here we investigated transcriptional reprogramming at genome-scale in mouse retroviral transplant models of acute myeloid leukaemia (AML using both gene-expression profiling and ChIP-sequencing. We identified several thousand candidate regulatory regions with altered levels of histone acetylation that were characterised by differential distribution of consensus motifs for key haematopoietic transcription factors including Gata2, Gfi1 and Sfpi1/Pu.1. In particular, downregulation of Gata2 expression was mirrored by abundant GATA motifs in regions of reduced histone acetylation suggesting an important role in leukaemogenic transcriptional reprogramming. Forced re-expression of Gata2 was not compatible with sustained growth of leukaemic cells thus suggesting a previously unrecognised role for Gata2 in downregulation during the development of AML. Additionally, large scale human AML datasets revealed significantly higher expression of GATA2 in CD34+ cells from healthy controls compared with AML blast cells. The integrated genome-scale analysis applied in this study represents a valuable and widely applicable approach to study the transcriptional control of both normal and aberrant haematopoiesis and to identify critical factors responsible for transcriptional reprogramming in human cancer.

  3. Tracer‐Based Metabolic NMR‐Based Flux Analysis in a Leukaemia Cell Line

    Science.gov (United States)

    Carrigan, John B.; Reed, Michelle A. C.; Ludwig, Christian; Khanim, Farhat L.; Bunce, Christopher M.

    2016-01-01

    Abstract High levels of reactive oxygen species (ROS) have a profound impact on acute myeloid leukaemia cells and can be used to specifically target these cells with novel therapies. We have previously shown how the combination of two redeployed drugs, the contraceptive steroid medroxyprogesterone and the lipid‐regulating drug bezafibrate exert anti‐leukaemic effects by producing ROS. Here we report a 13C‐tracer‐based NMR metabolic study to understand how these drugs work in K562 leukaemia cells. Our study shows that [1,2‐13C]glucose is incorporated into ribose sugars, indicating activity in oxidative and non‐oxidative pentose phosphate pathways alongside lactate production. There is little label incorporation into the tricarboxylic acid cycle from glucose, but much greater incorporation arises from the use of [3‐13C]glutamine. The combined medroxyprogesterone and bezafibrate treatment decreases label incorporation from both glucose and glutamine into α‐ketoglutarate and increased that for succinate, which is consistent with ROS‐mediated conversion of α‐ketoglutarate to succinate. Most interestingly, this combined treatment drastically reduced the production of several pyrimidine synthesis intermediates. PMID:27347458

  4. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

    Science.gov (United States)

    Puente, Xose S.; Pinyol, Magda; Quesada, Víctor; Conde, Laura; Ordóñez, Gonzalo R.; Villamor, Neus; Escaramis, Georgia; Jares, Pedro; Beà, Sílvia; González-Díaz, Marcos; Bassaganyas, Laia; Baumann, Tycho; Juan, Manel; López-Guerra, Mónica; Colomer, Dolors; Tubío, José M. C.; López, Cristina; Navarro, Alba; Tornador, Cristian; Aymerich, Marta; Rozman, María; Hernández, Jesús M.; Puente, Diana A.; Freije, José M. P.; Velasco, Gloria; Gutiérrez-Fernández, Ana; Costa, Dolors; Carrió, Anna; Guijarro, Sara; Enjuanes, Anna; Hernández, Lluís; Yagüe, Jordi; Nicolás, Pilar; Romeo-Casabona, Carlos M.; Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.; de Sanjosé, Silvia; Piris, Miguel A.; de Alava, Enrique; Miguel, Jesús San; Royo, Romina; Gelpí, Josep L.; Torrents, David; Orozco, Modesto; Pisano, David G.; Valencia, Alfonso; Guigó, Roderic; Bayés, Mónica; Heath, Simon; Gut, Marta; Klatt, Peter; Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.; Gut, Ivo; López-Guillermo, Armando; Estivill, Xavier; Montserrat, Emili; López-Otín, Carlos; Campo, Elías

    2012-01-01

    Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. PMID:21642962

  5. ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation

    Science.gov (United States)

    Hartmann, Luise; Dutta, Sayantanee; Opatz, Sabrina; Vosberg, Sebastian; Reiter, Katrin; Leubolt, Georg; Metzeler, Klaus H.; Herold, Tobias; Bamopoulos, Stefanos A.; Bräundl, Kathrin; Zellmeier, Evelyn; Ksienzyk, Bianka; Konstandin, Nikola P.; Schneider, Stephanie; Hopfner, Karl-Peter; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Middeke, Jan Moritz; Stölzel, Friedrich; Thiede, Christian; Wolf, Stephan; Bohlander, Stefan K.; Preiss, Caroline; Chen-Wichmann, Linping; Wichmann, Christian; Sauerland, Maria Cristina; Büchner, Thomas; Berdel, Wolfgang E.; Wörmann, Bernhard J.; Braess, Jan; Hiddemann, Wolfgang; Spiekermann, Karsten; Greif, Philipp A.

    2016-01-01

    The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the RUNX1/RUNX1T1 rearrangement. Despite the causative role of the RUNX1/RUNX1T1 fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring ZBTB7A mutations in 23% (13/56) of AML t(8;21) patients, including missense and truncating mutations resulting in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A. The transcription factor ZBTB7A is important for haematopoietic lineage fate decisions and for regulation of glycolysis. On a functional level, we show that ZBTB7A mutations disrupt the transcriptional repressor potential and the anti-proliferative effect of ZBTB7A. The specific association of ZBTB7A mutations with t(8;21) rearranged AML points towards leukaemogenic cooperativity between mutant ZBTB7A and the RUNX1/RUNX1T1 fusion. PMID:27252013

  6. The risks of leukaemia and other cancers in Seascale from radiation exposure

    International Nuclear Information System (INIS)

    Including new data in the radiation dose calculations for the Seascale study population of 1225 children and young persons, followed to 20 years of age or 1980, has, with modifications to dosimetric models, increased the predicted number of radiation-induced leukaemia resulting from Sallafield discharges from 0.01 to 0.016. Risk to the average child in the study, from the discharges, is now calculated as about 1 in 75,000 with a maximum risk of about 1 in 30,000 for children born in the mid-1950s. For the four fatal leukemias to be attributed to the Sellafield operations, the calculated average risk for all the children would have to be increased about 250 times. Estimate of the overall risk of radiation-induced leukaemia in the study population, from combined sources, has increased by less than 10% of the previous estimate and the total number of cases is still rounded to 0.1, as in R171. Risk to the average child is now calculated as about 1 in 12,250, about two thirds from natural background, 16% from Sellafield discharges, and 9% each from weapons fallout and medical exposure. (U.K.)

  7. Late cranial MRI after cranial irradiation in survivors of childhood cancer

    Energy Technology Data Exchange (ETDEWEB)

    Paeaekkoe, E. [Dept. of Diagnostic Radiology, Univ. of Oulu (Finland); Talvensaari, K. [Dept. of Pediatrics, Univ. of Oulu (Finland); Pyhtinen, J. [Dept. of Diagnostic Radiology, Univ. of Oulu (Finland); Lanning, M. [Dept. of Pediatrics, Univ. of Oulu (Finland)

    1994-11-01

    We carried out MRI on 43 survivors of childhood cancer after different treatment protocols with or without cranial radiotherapy. They were free of disease, therapy having been discontinued 2-20 years earlier. Treatment had been for various malignancies, excluding brain tumours; 27 had received cranial irradiation for acute lymphoblastic leukaemia (ALL) or lymphoma. Two asymptomatic young women treated for ALL had falx meningiomas. White matter changes, low intensity foci (representing calcification or old haemorrhage) and (heterogeneous intensity focic old haemorrhages) were seen only in patients who had undergone radiotherapy. Because of the possibility of benign, potentially curable brain tumours occurring after cranial irradiation, it may be wise to carry out occasional cranial imaging in the follow-up of these patients. No routine imaging follow-up is needed after chemotherapy alone. (orig.)

  8. DNA apoptosis and stability in B-cell chronic lymphoid leukaemia: implication of the DNA double-strand breaks repair system by non homologous recombination

    International Nuclear Information System (INIS)

    After an introduction presenting the diagnosis and treatment of chronic lymphoid leukaemia, its molecular and genetic characteristics, and its cellular origin and clonal evolution, this research thesis describes the apoptosis (definition and characteristics, cancer and chemotherapy, apoptotic ways induced by gamma irradiation), the genotoxic stresses, the different repair mechanisms for different damages, and the DNA repair processes. It reports how human chronic lymphocytic leukaemia B cells can escape DNA damage-induced apoptosis through the non-homologous end-joining DNA repair pathway, and presents non-homologous end-joining DNA repair as a potent mutagenic process in human chronic lymphocytic leukaemia B cells

  9. Phase 1 Dose- Escalation Trial of Clofarabine Followed by Escalating Dose of Fractionated Cyclophosphamide in Adults with Relapsed or Refractory Acute Leukaemias

    OpenAIRE

    Zeidan, Amer M.; Ricklis, Rebecca M.; Carraway, Hetty E.; Yun, Hyun D.; Greer, Jacqueline M.; Smith, B. Douglas; Levis, Mark J.; McDevitt, Michael A.; Pratz, Keith W.; Showel, Margaret M.; Gladstone, Douglas E; Gore, Steven D.; Judith E Karp

    2012-01-01

    The prognosis of patients with relapsed and refractory acute leukaemia (RRAL) is very poor. Forty patients with RRAL were enrolled (28 acute myeloid leukaemia [AML], 12 acute lymphoblastic leukaemia [ALL]) in this Phase 1 dose-escalation trial of daily-infused clofarabine (CLO) followed by cyclophosphamide (CY) for 4 consecutive days (CLO-CYx4). The median age was 48.5 years. The median number of prior regimens was 2 (range 1–5), and 6/40 patients (15%) had prior allogeneic haematopoietic ste...

  10. Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells

    DEFF Research Database (Denmark)

    Klitgaard, Josephine L; Koefoed, Klaus; Geisler, Christian;

    2013-01-01

    The treatment of chronic lymphocytic leukaemia (CLL) has been improved by introduction of monoclonal antibodies (mAbs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti-CD5 Abs that engage ...

  11. Transcriptional activation of immediate-early gene ETR101 by human T-cell leukaemia virus type I Tax

    DEFF Research Database (Denmark)

    Chen, Li; Ma, Shiliang; Li, Bo;

    2003-01-01

    Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate-early gene ETR101 expression in HTLV-I-infected cells and its regulation by Tax. ETR101 w...

  12. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with i>TP53 aberrations

    DEFF Research Database (Denmark)

    Farooqui, Mohammed Z H; Valdez, Janet; Martyr, Sabrina;

    2015-01-01

    BACKGROUND: Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53...

  13. Vincristine-induced apoptosis in vivo in peripheral blood mononuclear cells of children with acute lymphoblastic leukaemia (ALL)

    NARCIS (Netherlands)

    Groninger, E; Meeuwsen-de Boer, GJ; Sluiter, WJ; Poppema, S

    2000-01-01

    We conducted a study to demonstrate vincristine-induced apoptosis in vivo in peripheral blood mononuclear cells of children with newly diagnosed acute lymphoblastic leukaemia (ALL). In five children, apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP-digoxigenin nick-end la

  14. The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia

    DEFF Research Database (Denmark)

    O'Connor, C; Lohan, F; Campos, J;

    2016-01-01

    C/EBPα (p42 and p30 isoforms) is commonly dysregulated in cancer via the action of oncogenes, and specifically in acute myeloid leukaemia (AML) by mutation. Elevated TRIB2 leads to the degradation of C/EBPα p42, leaving p30 intact in AML. Whether this relationship is a cooperative event in AML...

  15. SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance.

    Directory of Open Access Journals (Sweden)

    V Adam Cruickshank

    Full Text Available Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated by its mutational spectrum as exerting a tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes.

  16. Prevention of infection in children with acute leukaemia - No major difference between total and selective bowel decontamination

    NARCIS (Netherlands)

    Muis, N; Kamps, WA

    1996-01-01

    To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non

  17. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Xu, Heng; Zhang, Hui; Yang, Wenjian;

    2015-01-01

    There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense varia...

  18. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia | Office of Cancer Genomics

    Science.gov (United States)

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden.

  19. Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Thomsen, C; Sørensen, P G; Karle, H;

    1987-01-01

    osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla...

  20. Reducing Childhood Obesity

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  1. Childhood vitiligo: Treatment paradigms

    Directory of Open Access Journals (Sweden)

    Amrinder Jit Kanwar

    2012-01-01

    Full Text Available Childhood vitiligo differs from the adults by showing a higher incidence in females, segmental vitiligo being more common and less frequent association with other systemic autoimmune and endocrine disorders.Childhood vitiligo is often associated with a marked psychosocial and long lasting effect on the self-esteem of the affected children and their parents, hence an adequate treatment is very essential. Treatment of vitiligo is indeed a tough challenge for the dermatologists′ more so in the background of childhood vitiligo. Although multiple therapeutic modalities are available in the therapeutic armamentarium, not all can be used in children. This brief report updates regarding various therapies available in the treatment of childhood vitiligo.

  2. Cardiovascular Conditions of Childhood

    Science.gov (United States)

    ... This childhood illness can result in long-term heart complications. Learn the symptoms, diagnosis and treatment for Kawasaki disease. Rheumatic Fever This inflammatory infection can occur after strep ...

  3. Childhood Immunization Schedule

    Science.gov (United States)

    ... Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get the ... See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of age ...

  4. Early Childhood Caries

    OpenAIRE

    Kawashita, Yumiko; Kitamura, Masayasu; Saito, Toshiyuki

    2011-01-01

    Dental caries is one of the most common childhood diseases, and people continue to be susceptible to it throughout their lives. Although dental caries can be arrested and potentially even reversed in its early stages, it is often not self-limiting and progresses without proper care until the tooth is destroyed. Early childhood caries (ECC) is often complicated by inappropriate feeding practices and heavy infection with mutans streptococci. Such children should be targeted with a professional ...

  5. Stress and childhood epilepsy

    OpenAIRE

    Campen, J.S. van

    2015-01-01

    Epilepsy is one of the most common chronic diseases in childhood, characterized by the enduring predisposition to generate epileptic seizures. Children with epilepsy and their parents often report seizures precipitated by stress. In order to increase our understanding of the pathophysiological mechanisms underlying the effects of stress on seizures in childhood epilepsy, we performed a variety of studies, which are described in this thesis. In part I we evaluate the extent of stress sensitivi...

  6. Childhood Ovarian Malignancy

    OpenAIRE

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-01-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4...

  7. Early childhood aggression

    OpenAIRE

    Alink, Lenneke Rosalie Agnes

    2006-01-01

    In this thesis the development, stability, and correlates of early childhood aggression were investigated. The normative development was examined in a general population sample using questionnaires completed by the parents of 12-, 24-, and 36-month-old children and again one year later. Results showed an early childhood aggression curve, with increasing rates of aggression in the second year of life and decreasing rates in the fourth year. One-year stabilities were moderate for 12-month-olds ...

  8. Pesticides and childhood cancers.

    OpenAIRE

    Daniels, J L; Olshan, A.F.; Savitz, D A

    1997-01-01

    To evaluate the possible association between pesticides and the risk of childhood cancers, epidemiologic studies published between 1970 and 1996 were critically reviewed. Thirty-one studies investigated whether occupational or residential exposure to pesticides by either parents or children was related to increased risk of childhood cancer. In general, the reported relative risk estimates were modest. Risk estimates appeared to be stronger when pesticide exposure was measured in more detail. ...

  9. Childhood cancer incidence in British Indians & Whites in Leicester, 1996-2008.

    Directory of Open Access Journals (Sweden)

    Shameq Sayeed

    Full Text Available BACKGROUND: South Asians in England have an increased risk of childhood cancer but incidence by their individual ethnicities using self-assigned ethnicity is unknown. Our objective was to compare the incidence of childhood cancer in British Indians and Whites in Leicester, which has virtually complete, self-assigned, ethnicity data and the largest population of Indians in England. METHODS: We obtained data on all cancer registrations from 1996 to 2008 for Leicester with ethnicity obtained by linkage to the Hospital Episodes Statistics database. Age-standardised incidence rates were calculated for childhood cancers in Indians and Whites as well as rate ratios, adjusted for age. RESULTS: There were 33 cancers registered among Indian children and 39 among White children. The incidence rate for Indians was greater compared to Whites for all cancers combined (RR 1.82 (95% CI 1.14 to 2.89; p = 0.01, with some evidence of increased risk of leukaemia (RR 2.20 (0.95 to 5.07; p = 0.07, lymphoma (RR 3.96 (0.99 to 15.84; p = 0.04 and central nervous system tumours (RR 2.70 (1.00 to 7.26; p = 0.05. Rates were also higher in British Indian children compared to children in India. CONCLUSIONS: British Indian children in Leicester had an increased risk of developing cancer compared to White children, largely due to a higher incidence of central nervous system and haematological malignancies.

  10. Influences of Childhood Experiences on Early Childhood Education Students

    OpenAIRE

    Strekalova-Hughes, Ekaterina; Maarouf, Saoussan; Keskin, Burhanettin

    2015-01-01

    This qualitative study examined whether or not childhood experiences of the early childhood education students affected their present personal beliefs and pedagogies. A digital survey was filled out by 58 students majoring in Early Childhood Education program. The participants were asked to identify and reflect on their impactful early experiences. The follow-up interviews with two participants were conducted to deepen the reflections on childhood experiences and explore their effects on the ...

  11. Methods and basic data of case-control study of leukaemia and lymphona among young people near Sellafield nuclear plant in West Cumbria

    International Nuclear Information System (INIS)

    The methods and basic data of a case-control study of leukaemia and lymphoma among young people near Sellafield are examined for reliability. Fifty-two cases of leukaemia, 22 of non-Hodgkin's lymphoma and 23 of Hodgkins disease occurring in people born in the area and diagnosed there in 1950-85 under the age of 25, and 1001 controls matched for sex and date of birth taken from the same birth registers were used in the study. (author)

  12. Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells

    OpenAIRE

    Rushworth, Stuart; Pillinger, Genevra; Abdul-Aziz, Amina; Piddock, Rachel; Shafat, Manar S.; Murray, Megan Y; Zaitseva, Lyubov; Lawes, Matthew J.; MacEwan, David J.; Bowles, Kristian M.

    2015-01-01

    Summary Background Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro. We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment. M...

  13. Childhood Eye Diseases and Conditions

    Science.gov (United States)

    ... Things College Students Should Do For Their Eyes Childhood Eye Diseases and Conditions Nov. 01, 2013 The ... cataract or eye disorder that needs treatment. Common Childhood Eye Diseases & Conditions When the following diseases are ...

  14. General Information about Childhood Ependymoma

    Science.gov (United States)

    ... without radiation therapy . Childhood ependymoma, anaplastic ependymoma, or RELA fusion–positive ependymoma Treatment of newly diagnosed childhood ... Grade II), anaplastic ependymoma (WHO Grade III), or RELA fusion–positive ependymoma is: Surgery . After surgery, the ...

  15. Treatment Option Overview (Childhood Ependymoma)

    Science.gov (United States)

    ... without radiation therapy . Childhood ependymoma, anaplastic ependymoma, or RELA fusion–positive ependymoma Treatment of newly diagnosed childhood ... Grade II), anaplastic ependymoma (WHO Grade III), or RELA fusion–positive ependymoma is: Surgery . After surgery, the ...

  16. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Nyvold, C; Madsen, H O; Ryder, L P;

    2000-01-01

    under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit......A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... to parts of the highly specific rearranged T-cell receptor delta (TCR-delta), T-cell receptor gamma (TCR-gamma), or immunoglobulin heavy chain (IgH) genes of the malignant clone. Using primers located externally to the restriction site the competitor and the DNA from the malignant clone will be amplified...

  17. Arthroplasties of hips and knees ankylosis in an adolescent with acute lymphoblastic leukaemia.

    Directory of Open Access Journals (Sweden)

    Dipo Samuel OLABUMUYI

    2011-10-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common malignancy in children, representing one third of all paediatric malignancies. Patients are often at high risk for complications due aggressive chemotherapy regimes required for treatment. Musculoskeletal complications include septic arthritis, osteonecrosis, osteoporosis, avascular necrosis and bony ankylosis. We report the case of a 16-year-old boy with ALL who developed osteonecrosis of multiple bones on a background of septicaemia, resulting in bony ankylosis of both hips and knees. He was treated with bilateral conversion of ankylosed hips (one hip to total hip replacement, the second hip to Girdlestone arthroplasty and bilateral ankylosed knees to total knee replacements. He remained well in remission five years after the last surgery. Our case highlights he possible musculoskeletal complications of ALL. 

  18. The development of integrated haematopathology laboratories: a new approach to the diagnosis of leukaemia and lymphoma.

    Science.gov (United States)

    Richards, S J; Jack, A S

    2003-12-01

    The diagnosis and monitoring of leukaemia and lymphoma requires the effective integration of a wide range of diagnostic techniques and expertise. The need to develop this type of service that crosses traditional boundaries of laboratory specialities is being recommended in national guidance. The Haematological Malignancy Diagnostic Service based within the Leeds Teaching Hospitals NHS Trust was established in 1993 to provide specialist laboratory services for the diagnosis of haematological malignancy for Yorkshire and Humberside in the UK. The department uses a wide range of methodologies including morphology, immunocytochemistry, flow cytometry and molecular genetics [fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR)] in a systematic and co-ordinated way. We describe how the department was established, its current working practices and highlight the advantages of an integrated laboratory for diagnosis of tumours of the haematopoietic system.

  19. Cytogenetic features of leukaemias diagnosed in residents of areas contaminated after the Chernobyl nuclear accident

    Energy Technology Data Exchange (ETDEWEB)

    Domracheva, E.V. E-mail: dom@blood.ru; Aseeva, E.A.; Obukhova, T.N.; Kobzev, Y.N.; Olshanskaya, Y.V.; D' achenko, L.V.; Udovichenko, A.I.; Zakharova, A.V.; Milyutina, G.I.; Nechai, V.V.; Vorobiov, A.I

    2000-05-15

    A comparison of chromosomal abnormalities in bone marrow leukaemic cells and of stable and unstable aberrations in lymphocytes of patients with hematological malignancies who live in areas with or without contamination by the Chernobyl nuclear accident has been made using FISH and G-banding. Healthy residents of these areas comprised the control group. No systematic cytogenetic differences of leukaemic cells between patients from contaminated and uncontaminated areas were observed. Lymphocyte aberrations, however, were generally higher in all subjects from contaminated areas. Comparison has been made with specific cytogenetic features of leukaemic cells and a high level of stable aberrations in lymphocytes of patients with secondary leukaemias that had developed after chemo- and/or radio-therapy.

  20. Drosophila: a model for studying genetic and molecular aspects of haematopoiesis and associated leukaemias

    Directory of Open Access Journals (Sweden)

    Michèle Crozatier

    2011-07-01

    Full Text Available Vertebrate haematopoietic stem cells (HSCs give rise to a hierarchically organised set of progenitors for erythroid, myeloid, lymphoid and megakaryocyte lineages, and are responsible for lifelong maintenance of the blood system. Dysregulation of the haematopoietic differentiation programme is at the origin of numerous pathologies, including leukaemias. With the discoveries that many transcriptional regulators and signalling pathways controlling blood cell development are conserved between humans and Drosophila melanogaster, the fruit fly has become a good model for investigating the mechanisms underlying the generation of blood cell lineages and blood cell homeostasis. In this review article, we discuss how genetic and molecular studies of Drosophila haematopoiesis can contribute to our understanding of the haematopoietic niche, as well as of the origin and/or progression of haematopoietic malignancies in humans.

  1. A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Russell, N H; Kjeldsen, L; Craddock, C;

    2015-01-01

    Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure...... is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35-44 years, either RIC or myeloablative conditioning was permitted. The aim...... was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50-0.85), P=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37...

  2. Detection of Bovine Leukaemia Virus Antibodies and Proviral DNA in Colostrum Replacers.

    Science.gov (United States)

    Choudhury, B; Finnegan, C; Phillips, A; Horigan, M; Pollard, T; Steinbach, F

    2015-10-01

    Great Britain has been bovine leukaemia virus (BLV) disease free since 1999. We recently reported three separate incidents of BLV seropositivity on farms with home-reared cattle due to the use of colostrum replacer rather than infection with BLV (Emerg. Infect. Dis., 19, 2013, 1027). These cases were all linked via the use of the same brand of colostrum replacer. Here, we investigate further by examining multiple brands of colostrum replacer for proviral DNA and BLV antibodies. BLV antibodies were detected in 7 of the colostrum replacers tested, with PCR concurring in two cases. Thus, the use of these BLV antibody-positive colostrum replacers may also lead to false-positive serological diagnostics. PMID:24268042

  3. Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M. (Haematological Department, Pesaro Hospital, Pesaro, Italy)

    1982-01-01

    2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20 % of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haemotopoietic recovery and the appearance of red cell isoenzyme phenotypes of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

  4. Auricular Oedema and Dyshidrotic Eczema in a Patient with Acute Myeloid Leukaemia Treated with Cytarabine

    Directory of Open Access Journals (Sweden)

    K. Brandt

    2010-10-01

    Full Text Available Cytarabine is an effective drug in the treatment of haematological malignancies. The therapy is associated with various complications. Frequencies of dermatological side-effects range from 2–72% and occur most commonly after high-dose regimens. Although most cutaneous reactions are mild and resolve spontaneously within several days, they may result in an increased risk of infection and alterations in comfort. In some cases, severe life-threatening reactions have been reported. Here we describe the case of a patient with acute myeloid leukaemia, who developed severe exceptional skin toxicity in terms of auricular oedema and palmar dyshidrotic eczema after the application of low-dose cytarabine. Re-administration of the drug resulted in reduced skin toxicity during further cycles of chemotherapy. Negative epicutaneous patch-testing supported the existence of cytarabine-provoked toxicity.

  5. Childhood trauma in bipolar disorder

    OpenAIRE

    Watson, S; Gallagher, P.; Dougall, D.; R Porter; Moncrieff, J.; Ferrier, I. N.; Young, A. H.

    2014-01-01

    Objective: There has been little investigation of early trauma in bipolar disorder despite evidence that stress impacts on the course of this illness. We aimed to compare the rates of childhood trauma in adults with bipolar disorder to a healthy control group, and to investigate the impact of childhood trauma on the clinical course of bipolar disorder. Methods: Retrospective assessment of childhood trauma was conducted using the Childhood Trauma Questionnaire (CTQ) in 60 outpatients with bipo...

  6. In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Yusuke; Okubo, Toshiyuki [University of Tokyo, Department of Radiology, Institute of Medical Science, Tokyo (Japan); Tojo, Arinobu; Sekine, Rieko; Soda, Yasushi; Kobayashi, Seiichiro; Nomura, Akiko; Izawa, Kiyoko [University of Tokyo, Division of Molecular Therapy, Advanced Clinical Research Centre, Tokyo (Japan); Kitamura, Toshio [University of Tokyo, Division of Cellular Therapy, Advanced Clinical Research Centre, Tokyo (Japan); Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Tokyo (Japan)

    2006-05-15

    The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells. Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage. The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells. Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity. (orig.)

  7. Stem cell targets and dosimetry for radiation-induced leukaemia and bone cancer

    International Nuclear Information System (INIS)

    The ICRP are proposing changes to the assumed targets for the induction of bone cancer and leukaemias as described by Harrison et al in an accompanying article. This study of radiation targets in the skeleton finds that the endosteum of the long bone medullary cavities is not an important target, especially in the adult, as it supports a very low stem cell population associated with high adiposity, whereas the periosteum has a strong mesenchymal stem cell population throughout lifetime. Quiescent stem cells are found to be preferentially located close to the trabecular bone surface in the osteoblastic niche, whereas progenitors of stem cells prefer to reside in perivascular niches. Evidence is given in support of the suggestion that the absence of excess bone-cancer in atomic bomb survivors may be related to the extremely low prevalence of Paget's disease in Japan. The hypoxic conditions of the endosteum adjacent to quiescent bone surfaces provide a radioprotective stem cell microenvironment by a factor of 2-3 fold, whereas greater radiosensitivity is prevalent in the young and individuals with benign diseases of bone. Increasing the volume of the bone cancer target from a 10 μm thick endosteum to a 50 μm peripheral marrow layer will result in an approximately three-fold decline in the mean dose from alpha-emitters in bone. These new observations are shown to go some way in explaining the low incidences for leukaemia and especially bone cancer in radium dial painters, Thorotrast patients and Mayak nuclear workers. (author)

  8. Stem cell targets and dosimetry for radiation-induced leukaemia and bone cancer

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, R.B., E-mail: richardr@aecl.ca

    2007-07-01

    The ICRP are proposing changes to the assumed targets for the induction of bone cancer and leukaemias as described by Harrison et al in an accompanying article. This study of radiation targets in the skeleton finds that the endosteum of the long bone medullary cavities is not an important target, especially in the adult, as it supports a very low stem cell population associated with high adiposity, whereas the periosteum has a strong mesenchymal stem cell population throughout lifetime. Quiescent stem cells are found to be preferentially located close to the trabecular bone surface in the osteoblastic niche, whereas progenitors of stem cells prefer to reside in perivascular niches. Evidence is given in support of the suggestion that the absence of excess bone-cancer in atomic bomb survivors may be related to the extremely low prevalence of Paget's disease in Japan. The hypoxic conditions of the endosteum adjacent to quiescent bone surfaces provide a radioprotective stem cell microenvironment by a factor of 2-3 fold, whereas greater radiosensitivity is prevalent in the young and individuals with benign diseases of bone. Increasing the volume of the bone cancer target from a 10 {mu}m thick endosteum to a 50 {mu}m peripheral marrow layer will result in an approximately three-fold decline in the mean dose from alpha-emitters in bone. These new observations are shown to go some way in explaining the low incidences for leukaemia and especially bone cancer in radium dial painters, Thorotrast patients and Mayak nuclear workers. (author)

  9. In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

    International Nuclear Information System (INIS)

    The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells. Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage. The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells. Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity. (orig.)

  10. Discovering the Culture of Childhood

    Science.gov (United States)

    Plank, Emily

    2016-01-01

    We often filter our interactions with children through the lens of adulthood. View the culture of childhood through a whole new lens. Identify age-based bias and expand your outlook on and understanding of early childhood as a culture. Examine various elements of childhood culture: language, the power of believing, artistic expressions, and social…

  11. Reconceptualizing the "Nature" of Childhood

    Science.gov (United States)

    Taylor, Affrica

    2011-01-01

    This interdisciplinary article draws upon human geography to bring fresh new perspectives to the relationship between two commonly conflated concepts: "childhood" and "nature". Childhood studies scholars have gone a long way towards retheorizing childhood beyond the "natural" and the "universal" by pointing to its historical and cultural…

  12. Childhood myelodysplastic syndrome.

    Science.gov (United States)

    Chatterjee, Tathagata; Choudhry, V P

    2013-09-01

    Myelodysplastic syndrome (MDS) comprises of a heterogeneous group of bone marrow disorders resulting from a clonal stem cell defect characterised by cytopenias despite a relatively hypercellular marrow, ineffective hematopoiesis, morphological dysplasia in the marrow elements, no response to hematinics such as iron, B12 or folic acid and risk of progression to leukemia. Myelodysplastic syndrome in childhood is extremely rare and accounts for less than 5% of all hematopoietic neoplasms in children below the age of 14 y. The primary MDS in children, also known as de novo MDS differs from secondary MDS which generally follows congenital or acquired bone marrow (BM) failure syndromes as well as from therapy related MDS, commonly resulting from cytotoxic therapy. MDS associated with Down syndrome which accounts for approximately one-fourth of cases of childhood MDS is now considered a unique biologic entity synonymous with Down syndrome-related myeloid leukemia and is biologically distinct from other cases of childhood MDS. Refractory cytopenia of childhood (RCC) is the commonest type of MDS. Genetic changes predisposing to MDS in childhood remain largely obscure. Monosomy 7 is by-far the commonest cytogenetic abnormality associated with childhood MDS; however most cases of RCC show a normal karyotype. Complex cytogenetic abnormalities and trisomy 8 and trisomy 21 are also occasionally observed. The most effective and curative treatment is Hematopoietic stem cell transplantation and this is particularly effective in children with the monosomy 7 genetic defect as well as those displaying complex karyotype abnormalities provided it is instituted early in the course of the disease.

  13. A Tewo Tibetan Childhood

    Directory of Open Access Journals (Sweden)

    Rdo rje tshe brtan

    2013-04-01

    Full Text Available Rdo rje tshe brtan (b. 1986 describes his childhood in Dredze Village, Yiwa Township, Tewo County, Gannan Tibetan Autonomous Prefecture, Gansu Province, China, as well as being a student in Xining City, Qinghai Province. Topics covered include his family, childhood injuries and illnesses, education, Terang (malicious household deities, mountain deities and associated rituals and sacrifices, death, conflict with other locals, collecting local plants, a birth in the village, stealing fruit, a wedding, plowing, a visit to a hot spring, a lost yak, slaughtering pigs, government confiscation of fields, and slaughtering pigs. Photos provide additional detail.

  14. Myeloid leukaemia frequency after protracted exposure to ionizing radiation: experimental confirmation of the flat dose-response found in ankylosing spondylitis after a single treatment course with x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Mole, R.H.; Major, I.R. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

    1983-01-01

    The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally ..gamma..-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

  15. Haematological malignancies in childhood in Croatia: Investigating the theories of depleted uranium, chemical plant damage and 'population mixing'

    International Nuclear Information System (INIS)

    Some of potential causes proposed to explain the reported increase of haematological malignancies in childhood during or after the war period in several countries include depleted uranium, chemical pollution and population mixing theory. The aim of this study was to define the population of Croatian children aged 0-14 years who were potentially exposed to each of those risks during the war and to investigate any possible association between the exposure and the incidence of haematological malignancies. The authors analyzed the data reported by the Cancer Registry of Croatia during the pre-war period (1986-1990), war period (1991-1995) and post-war period (1996-1999). In the group of 10 counties potentially exposed to depleted uranium and two counties where chemical war damage occurred, no significant difference in incidence of the studied haematological malignancies was noted in comparison to pre-war period. The incidence of lymphatic leukaemia significantly increased in four counties where population mixing had occurred during the war period, supporting the 'mixing theory'. In those counties, the incidence of Hodgkin's lymphoma decreased during and after the war. In Croatia as a whole, decreases in incidence of myeloid leukaemias during war and non-Hodgkin lymphoma after the war were noted

  16. A Fatal Case of Acute Myeloid Leukaemia-Methotrexate Related or Primary Autoimmune Disease Related: A Rare Case Report.

    Science.gov (United States)

    Agarwal, Saurabh; Kaeley, Nidhi; Gupta, Priyanka; Gupta, Vibha; Bhatia, Rohan

    2016-03-01

    Methotrexate is being used for many years in the treatment of chronic medical disorders e.g. rheumatoid arthritis since 1951. It has been associated with various systemic toxicities and complications including bone marrow suppression and lymphomas. The development of leukaemia in a patient of chronic rheumatoid arthritis is either related with the primary disease or due to the drugs which are used in the treatment like cyclophosphamide. In our present case, a 70-year-old female who was a known case of Rheumatoid Arthritis (RA) and was on methotrexate once a week orally for the past 20 years presented with complaints of loss of appetite, loss of weight and anaemia since 2 months. After thorough examination and investigation, she was diagnosed with acute myeloid leukaemia (AML-M4) with bilateral chest consolidation. PMID:27134915

  17. Early Childhood Trauma

    Science.gov (United States)

    National Child Traumatic Stress Network, 2010

    2010-01-01

    Early childhood trauma generally refers to the traumatic experiences that occur to children aged 0-6. Because infants' and young children's reactions may be different from older children's, and because they may not be able to verbalize their reactions to threatening or dangerous events, many people assume that young age protects children from the…

  18. 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 was re...

  19. Childhood disintegrative disorder

    DEFF Research Database (Denmark)

    Mouridsen, Svend Erik

    2003-01-01

    are sometimes associated with this disorder, but contrary to earlier belief this is not typical. Interest in childhood disintegrative disorder has increased markedly in recent years and in this review attention is given to more recently published cases based on ICD-9, ICD-10 and DSM-IV diagnostic systems...

  20. Managing childhood obesity

    Science.gov (United States)

    The prevalence of childhood obesity has steadily increased over the last decades, with approximately 35% of children aged 6-19 classified as overweight or obese. Recently, a plateau in the increasing rates of obesity has been observed. Despite this leveling off, overweight and obese children are hea...

  1. Atopic endotype in childhood

    DEFF Research Database (Denmark)

    Schoos, Ann-Marie Malby; Chawes, Bo Lund Krogsgaard; Rasmussen, Morten Arendt;

    2016-01-01

    with asthma through early childhood (0-6 years) when analyzed as any sensitization (odds ratio [OR] range, 0.78-1.29; P ≥ .48). However, at 13 years of age, any sensitization was associated with asthma (OR range, 4.02-5.94; all P contrast, any sensitization was associated with eczema at ½, 1...

  2. Early Childhood Education 193.

    Science.gov (United States)

    Polis, Gloria Owens

    This module adapts the content of an on-campus early childhood education program to a competency-based set of self-paced learning activities for use in largely self-directed, supervised instruction of student child caretakers employed at such settings as a day care center or Head Start agency. Addressed in the individual sections of the module are…

  3. Conscientiousness: Origins in Childhood?

    Science.gov (United States)

    Eisenberg, Nancy; Duckworth, Angela L.; Spinrad, Tracy L.; Valiente, Carlos

    2014-01-01

    In this review, we evaluate developmental and personality research with the aim of determining whether the personality trait of conscientiousness can be identified in children and adolescents. After concluding that conscientiousness does emerge in childhood, we discuss the developmental origins of conscientiousness with a specific focus on…

  4. Childhood environment and obesity

    Science.gov (United States)

    US children are at risk for developing childhood obesity. Currently, 23% of children ages 2–5 are overweight or obese, i.e., at or above the 85th percentile. This prevalence becomes even higher as children age, with 34% of children ages 6–11 being overweight or obese. Ethnic minority children are at...

  5. Childhood Obesity: An Overview

    Science.gov (United States)

    Reilly, John J.

    2007-01-01

    This article reviews recent research evidence, largely from systematic reviews, on a number of aspects of childhood obesity: its definition and prevalence; consequences; causes and prevention. The basis of the body mass index (BMI) as a means of defining obesity in children and adolescents is discussed: a high BMI for age constitutes obesity. In…

  6. Childhood microbial keratitis

    Directory of Open Access Journals (Sweden)

    Abdullah G Al Otaibi

    2012-01-01

    Conclusion: Children with suspected microbial keratitis require comprehensive evaluation and management. Early recognition, identifying the predisposing factors and etiological microbial organisms, and instituting appropriate treatment measures have a crucial role in outcome. Ocular trauma was the leading cause of childhood microbial keratitis in our study.

  7. Early childhood aggression

    NARCIS (Netherlands)

    Alink, Lenneke Rosalie Agnes

    2006-01-01

    In this thesis the development, stability, and correlates of early childhood aggression were investigated. The normative development was examined in a general population sample using questionnaires completed by the parents of 12-, 24-, and 36-month-old children and again one year later. Results show

  8. Transmembrane signalling via HLA-DR molecules on T cells from a Sezary T-cell leukaemia line

    DEFF Research Database (Denmark)

    Geisler, C; Kuhlmann, J; Møller, T;

    1990-01-01

    The human Sezary T-cell leukaemia line, HUT.78, represents a population of activated T cells, i.e. they are HLA-DR+ and IL-2R+. We have analysed the capacity of HUT.78 cells (1) to stimulate HLA-DR-specific T-cell lines or clones and (2) to be induced to synthesize IL-2 by anti-HLA-DR monoclonal...

  9. Myelin repair in vivo is increased by targeting oligodendrocyte precursor cells with nanoparticles encapsulating leukaemia inhibitory factor (LIF)

    OpenAIRE

    Rittchen, Sonja; Boyd, Amanda; Burns, Alasdair; Park, Jason; Fahmy, Tarek M.; Metcalfe, Su; Williams, Anna

    2015-01-01

    Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system (CNS). Many nerve axons are insulated by a myelin sheath and their demyelination not only prevents saltatory electrical signal conduction along the axons but also removes their metabolic support leading to irreversible neurodegeneration, which currently is untreatable. There is much interest in potential therapeutics that promote remyelination and here we explore use of leukaemia inhibitory factor (LI...

  10. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria

    International Nuclear Information System (INIS)

    The raised incidence of leukaemia, particularly, and non-Hodgkin's lymphoma among children near Sellafield was associated with paternal employment and recorded external dose of whole body penetrating radiation during work at the plant before conception. The association can explain statistically the observed geographical excess. This result suggests an effect of ionising radiation on fathers that may be leukaemogenic in their offspring, though other, less likely, explanations are possible. (author)

  11. Inhibition of proliferation by agricultural plant extracts in seven human adult T-cell leukaemia (ATL)-related cell lines.

    Science.gov (United States)

    Kai, Hisahiro; Akamatsu, Ena; Torii, Eri; Kodama, Hiroko; Yukizaki, Chizuko; Sakakibara, Yoichi; Suiko, Masahito; Morishita, Kazuhiro; Kataoka, Hiroaki; Matsuno, Koji

    2011-07-01

    Adult T-cell leukaemia (ATL) is caused by human T-cell leukaemia virus type I (HTLV-I) infection and is resistant to conventional chemotherapy. We evaluated the inhibitory effects of agricultural plants on the proliferation of seven ATL-related human leukaemia cells, using three ATL cell lines (ED, Su9T01 and S1T), two human T-cell lines transformed by HTLV-I infection (HUT-102 and MT-2) and two HTLV-I-negative human T-cell acute lymphoblastic leukaemia cell lines (Jurkat and MOLT-4). A total of 52 samples of 80% ethanol extracts obtained from 30 types of agricultural plants were examined. On the basis of IC(50) values, we selected samples with greater activity than genistein, which was used as a positive control. The highest inhibitory effect was observed with extracts from leaves of Vaccinium virgatum Aiton (blueberry) on four cell lines (ED, Su9T01, HUT-102 and Jurkat); seeds of Momordica charantia L. (bitter gourd) exhibited the second highest activity. The bitter gourd seeds suppressed the proliferation of three cell lines (Su9T01, HUT-102 and Jurkat). The extracts from edible parts of Ipomea batatas LAM. (sweet potato), edible parts of Colocasia esculenta (L.) Schott (taro), skin of taro and seeds of Prunus mume Sieb. et Zucc. (mume) showed markedly greater inhibitory effects on Su9T01 than genistein. These findings suggest that ATL-preventative bioactive compounds may exist in these agricultural plants, which are considered to be functional foods. PMID:21293936

  12. SWOG S0910: A Phase 2 Trial of Clofarabine/Cytarabine/Epratuzumab for Relapsed/Refractory Acute Lymphocytic Leukaemia

    OpenAIRE

    Advani, Anjali S; McDonough, Shannon; Coutre, Steven; Wood, Brent; Radich, Jerald; Mims, Martha; O’Donnell, Margaret; Elkins, Stephanie; Becker, Michael; Othus, Megan; Appelbaum, Frederick R.

    2014-01-01

    Precursor B-acute lymphoblastic leukaemias (pre-B ALLs) comprise the majority of ALLs and virtually all blasts express CD22 in the cytoplasm and on the cell surface. In the present study (Southwestern Oncology Group S0910), we evaluated the addition of epratuzumab, a humanized monoclonal antibody against CD22, to the combination of clofarabine and cytarabine in adults with relapsed/refractory pre-B ALL. The response rate [complete remission and complete remission with incomplete count recover...

  13. The BTK Inhibitor Ibrutinib (PCI-32765) Blocks Hairy Cell Leukaemia Survival, Proliferation and BCR Signalling: A New Therapeutic Approach

    OpenAIRE

    Sivina, Mariela; Kreitman, Robert J.; Arons, Evgeny; Ravandi, Farhad; Burger, Jan A.

    2014-01-01

    B cell receptor (BCR) signalling plays a critical role in the progression of several B-cell malignancies, but its role in hairy cell leukaemia (HCL) is ambiguous. Bruton tyrosine kinase (BTK), a key player in BCR signalling, migration and adhesion, can be targeted with ibrutinib, a selective, irreversible BTK inhibitor. We analysed BTK expression and function in HCL and analysed the effects of ibrutinib on HCL cells. We demonstrated uniform BTK protein expression in HCL cells. Ibrutinib signi...

  14. Stable expression of promyelocytic leukaemia (PML) protein in telomerase positive MCF7 cells results in alternative lengthening of telomeres phenotype

    OpenAIRE

    Yong Jacklyn W Y; Yeo Xiujun; Khan Md; Lee Martin B; Prakash Hande M

    2012-01-01

    Abstract Background Cancer cells can employ telomerase or the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. Cancer cells that use the ALT pathway exhibit distinct phenotypes such as heterogeneous telomeres and specialised Promyelocytic leukaemia (PML) nuclear foci called APBs. In our study, we used wild-type PML and a PML mutant, in which the coiled-coil domain is deleted (PML C/C-), to investigate how these proteins can affect telomere maintenance pathways in c...

  15. Effect of age on 6-mercaptopurine metabolic profile during the maintenance phase in children with acute lymphoblastic leukaemia

    Institute of Scientific and Technical Information of China (English)

    DZHANGt; AGILBER; KYAKOUBEN; YMEDARD; EVILMER; EJACQZ-AIGRAIN

    2004-01-01

    INTRODUCTION: 6-Mercaptopurine (6-MP) is a thiopurine analogue administered for the treatment of acute lymphoblastic leukaemia (ALL). It is an inactive pro-drug that undergoes extensive metabolism resulting in the formation of active metabolites 6-thioguanine nucleotides (6-TGN) and inactive 6-mercaptopurine methylated metabolites (6-MMP) under the genetic control of the enzyme thiopurine methyltransferase (TPMT). 6-MP metabolic profile (6-MMP/6-TGN) was proposed as a tool to

  16. Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens.

    OpenAIRE

    Ingram, L; Mott, M G; Mann, J R; Raafat, F; Darbyshire, P J; Morris Jones, P. H.

    1987-01-01

    Eight children treated between 1977 and 1983 with the UK Children's Cancer Study Group's non-Hodgkin lymphoma (NHL) and T-cell protocols have developed second malignancies within 7 years of commencing treatment. Five developed acute non-lymphoblastic leukaemia and a sixth died from infection while pancytopenic with a pre-leukaemic marrow. The other malignancies were cerebral astrocytoma and an undifferentiated low grade sarcoma. These eight children were included among 261 children studied in...

  17. Dietary Phenolic Acids Act as Effective Antioxidants in Membrane Models and in Cultured Cells, Exhibiting Proapoptotic Effects in Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Laura Zambonin

    2012-01-01

    Full Text Available Caffeic, syringic, and protocatechuic acids are phenolic acids derived directly from food intake or come from the gut metabolism of polyphenols. In this study, the antioxidant activity of these compounds was at first evaluated in membrane models, where caffeic acid behaved as a very effective chain-breaking antioxidant, whereas syringic and protocatechuic acids were only retardants of lipid peroxidation. However, all three compounds acted as good scavengers of reactive species in cultured cells subjected to exogenous oxidative stress produced by low level of H2O2. Many tumour cells are characterised by increased ROS levels compared with their noncancerous counterparts. Therefore, we investigated whether phenolic acids, at low concentrations, comparable to those present in human plasma, were able to decrease basal reactive species. Results show that phenolic acids reduced ROS in a leukaemia cell line (HEL, whereas no effect was observed in normal cells, such as HUVEC. The compounds exhibited no toxicity to normal cells while they decreased proliferation in leukaemia cells, inducing apoptosis. In the debate on optimal ROS-manipulating strategies in cancer therapy, our work in leukaemia cells supports the antioxidant ROS-depleting approach.

  18. Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013

    Science.gov (United States)

    Yeoh, Allen EJ; Tan, Daryl; Li, Chi-Kong; Hori, Hiroki; Tse, Eric; Pui, Ching-Hon

    2014-01-01

    The survival rates for both adult and children with acute lymphoblastic leukaemia have improved substantially in recent years with wider use of improved risk-directed therapy and supportive care. In nearly all developed countries, clinical practice guidelines have been formulated by multidisciplinary panels of leukaemia experts, with the goal of providing recommendations on standard treatment approaches based on current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, there are huge disparities in economy and infrastructure among the countries, and even among different regions in some large countries. This review summarizes the recommendations developed for Asian countries by a panel of adult and paediatric leukaemia therapists, based on the availability of financial, skill and logistical resources, at a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand. The management strategies described here are stratified by a four-tier system (basic, limited, enhanced and maximum) based on the resources available to a particular country or region. PMID:24176570

  19. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia.

    Science.gov (United States)

    Irvine, David A; Zhang, Bin; Kinstrie, Ross; Tarafdar, Anuradha; Morrison, Heather; Campbell, Victoria L; Moka, Hothri A; Ho, Yinwei; Nixon, Colin; Manley, Paul W; Wheadon, Helen; Goodlad, John R; Holyoake, Tessa L; Bhatia, Ravi; Copland, Mhairi

    2016-01-01

    Targeting the Hedgehog (Hh) pathway represents a potential leukaemia stem cell (LSC)-directed therapy which may compliment tyrosine kinase inhibitors (TKIs) to eradicate LSC in chronic phase (CP) chronic myeloid leukaemia (CML). We set out to elucidate the role of Hh signaling in CP-CML and determine if inhibition of Hh signaling, through inhibition of smoothened (SMO), was an effective strategy to target CP-CML LSC. Assessment of Hh pathway gene and protein expression demonstrated that the Hh pathway is activated in CD34(+) CP-CML stem/progenitor cells. LDE225 (Sonidegib), a small molecule, clinically investigated SMO inhibitor, used alone and in combination with nilotinib, inhibited the Hh pathway in CD34(+) CP-CML cells, reducing the number and self-renewal capacity of CML LSC in vitro. The combination had no effect on normal haemopoietic stem cells. When combined, LDE225 + nilotinib reduced CD34(+) CP-CML cell engraftment in NSG mice and, upon administration to EGFP(+) /SCLtTA/TRE-BCR-ABL mice, the combination enhanced survival with reduced leukaemia development in secondary transplant recipients. In conclusion, the Hh pathway is deregulated in CML stem and progenitor cells. We identify Hh pathway inhibition, in combination with nilotinib, as a potentially effective therapeutic strategy to improve responses in CP-CML by targeting both stem and progenitor cells. PMID:27157927

  20. Leukaemia and thyroid cancer in emergency workers of the Chernobyl accident:. Estimation of radiation risks (1986-1995)

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, V.K. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation); Tsyb, A.F. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation); Gorsky, A.I. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation); Maksyutov, M.A. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation); Rastopchin, E.M. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation); Konogorov, A.P. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation); Korelo, A.M. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation); Biryukov, A.P. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation); Matyash, V.A. [Russian Academy of Medical Sciences, Medical Radiological Research Center, Obninsk (Russian Federation)

    1997-02-01

    This work focuses on the direct epidemiological assessment of the risks of radiation-induced leukaemia and thyroid cancer in emergency workers (EW) after the Chernobyl accident. The Russian National Medical Dosimetric Registry (RNMDR) contains data for 168 000 EW as of January 1, 1996. The analysis relates to 48 leukaemias and 47 thyroid cancers, diagnosed and verified. Radiation risks are estimated by comparing the EW data with national data for a male population of the same age distribution. For leukaemia, an excess relative risk per Gy (ERR/Gy) of 4.30 (95% CI: 0.83, 7.75) is obtained, while the excess absolute risk per 10{sup 4} person-years (PY) Gy (EAR/10{sup 4} PY Gy) is found to be 1.31 (95% CI: 0.23, 2.39); for thyroid cancer an ERR/Gy of 5.31 (95% CI: 0.04, 10.58) is obtained, and an EAR/10{sup 4} PY Gy of 1.15 (95% CI: 0.08, 2.22). (orig.). With 9 figs., 10 tabs.

  1. The effect of dietary intake changes on nutritional status in acute leukaemia patients after first induction chemotherapy.

    Science.gov (United States)

    Malihi, Z; Kandiah, M; Chan, Y M; Esfandbod, M; Vakili, M; Hosseinzadeh, M; Zarif Yeganeh, M

    2015-07-01

    This study aimed to evaluate how changes in dietary intake among acute lymphoblastic and acute myeloid leukaemia (ALL and AML) patients affect nutritional status after the first induction chemotherapy. Dietary intake was assessed using 24-h recall and a 136-item food frequency questionnaire. Nutritional status was assessed by Patients Subjective Global Assessment questionnaire before starting induction therapy and again after 1 month. All newly diagnosed acute leukaemia patients aged 15 years old and older who attended three referral hospitals for initiation of their induction chemotherapy were included in the sample selection provided that they gave informed consent. A total of 30 AML and 33 ALL patients participated in the study. Dietary intake and nutritional status worsened after the chemotherapy treatment. Dietary intake in terms of macronutrients, micronutrients, food variety and diet diversity score changed significantly after the induction chemotherapy. No significant relationship was found between the changes in dietary indices and nutritional status. Chemotherapy-related side effects as an additional factor to cancer itself could affect dietary intake of leukaemia patients. The effectiveness of an early assessment of nutritional status and dietary intake should be further investigated in order to deter further deterioration.

  2. Evolution of procalcitonin, C-reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis.

    Science.gov (United States)

    Roques, Marjorie; Chretien, Marie Lorraine; Favennec, Camille; Lafon, Ingrid; Ferrant, Emmanuelle; Legouge, Caroline; Plocque, Alexia; Golfier, Camille; Duvillard, Laurence; Amoureux, Lucie; Bastie, Jean Noel; Maurin-Bernier, Lory; Dalle, Frederic; Caillot, Denis

    2016-06-01

    Unlike bacterial infections, the value of procalcitonin (PCT) in detecting fungal infections in leukaemia patients is not clear. To determine whether the monitoring of PCT coupled with C-reactive protein (CRP) and fibrinogen (Fib) could be helpful in the management of pulmonary aspergillosis (IPA) or mucormycosis (PM), we retrospectively analysed the evolution of PCT, CRP and Fib levels in 94 leukaemia patients with proven/probable IPA (n = 77) or PM (n = 17) from D-12 to D12 relative to IFI onset defined as D0. Overall, 2140 assays were performed. From D-12 to D0, 12%, 5% and 1.4% of patients had PCT >0.5, 1 and 1.5 μg l(-1) , respectively, while CRP was >50, 75 and 100 mg l(-1) in 84%, 70% and 57% and Fib was >4, 5 and 6 g l(-1) in 96%, 80% and 61% of cases respectively (P 1.5 μg l(-1) , while CRP >100 mg l(-1) and Fib >6 g l(-1) were observed in 80% and 75% of cases respectively (P < 10(-7) ). In leukaemia patients, IPA or PM was accompanied by a significant increase in CRP and Fib while PCT remained low. PMID:26931315

  3. Distinct morphophenotypic features of chronic B-cell leukaemias identified with CD1c and CD23 antibodies.

    Science.gov (United States)

    Orazi, A; Cattoretti, G; Polli, N; Delia, D; Rilke, F

    1991-07-01

    Morphological criteria usually applied to diagnose various subtypes of B-cell chronic lymphoid leukaemia are largely subjective. Immunophenotyping of 61 relevant cases using a selected panel of monoclonal antibodies (mAb), showed that CD1c and CD23 mAb were able to separate B-cell chronic lymphocytic leukaemia (B-CLL) from other chronic B-cell lymphoproliferative diseases. Lymphocytes of B-CLL were CD1c-, CD23+, whereas those of other types of chronic B-cell leukaemia were CD1c+/-, CD23-, and CD38/-. Non-B-CLL cases had a significantly higher amount of large peroxidase-negative (unstained) cells analyzed with an automated blood cell counter (Technicon H6000). This type of volumetric assessment allowed a separation between typical and "atypical" B-CLL, which otherwise were both CD1c-, and CD23+. These combinations of phenotypic markers corresponded to well-defined haematopathologic entities, conventionally diagnosed on peripheral blood (PB) and bone marrow smears, and on histologic sections of lymph nodes and spleen.

  4. Fludarabine and cytarabine combined chemotherapy followed by transfusion of donor blood stem cells for treating relapse of acute leukaemia after allogeneic haematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    YOU Yong; LI Qiu-bai; CHEN Zhi-chao; LI Wei-ming; XIA Ling-hui; ZHOU Hao; ZOU Ping

    2008-01-01

    Background Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation (alIo-HSCT) for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after alIo-HSCT.Methods Seven patients, median age 34 years, with relapse of acute leukaemia after alIo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days. Five patients suffered from acute myeloid leukaemia (2 refractory) and 2 refractory acute lymphoblastic leukaemia. After the transplantation, the median relapse time was 110 days (range,38-185 days). Two days after chemotherapy, 5 patients received infusion of donor's peripheral blood stem cells, mobilized by granulocyte colony stimulating factor. No prophylactic agents of graft versus host diseases were administered.Results Six patients achieved haematopoietic reconstitution. DNA sequence analysis at day 30 after treatment identified all as full donor chimera type. The median observation time was 189 days. After the treatment, the median time for neutrophilic granulocyte value ≥0.5x109/L and for platelet value >20x109/L were 13 days (range, 10-18 days) and 15 days (range, 11-24 days), respectively. Graft versus host disease occurred in 2 patients (acute) and 3 (chronic). Five patients suffered from pulmonary fungal infection (2 died), 3 haemorrhagic cystitis and 2 cytomegalovirus viraemia. The other patients died of leukaemia related deaths. Three patients with chronic graft versus host disease who had received donor peripheral blood stem cells reinfusion have survived for 375 days, 232 days and 195 days, respectively.Conclusions Fludarabine with cytarabine plus the donor haematopoietic stem cell should be considered as an effective therapeutic regimen for relapse of acute leukaemia after alIo-HSCT. The disease free state of patients may increase, thou.gh with

  5. Late mortality among five-year survivors of cancer in childhood and adolescence

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, Torgil R.; Garwicz, Stanislaw; Perfekt, Roland; Barlow, Lotti; Falck Winther, Jeanette; Glattre, Eystein; Olafsdottir, Gudridur; Olsen, Joergen H.; Ritvanen, Annukka; Sankila, Risto [Univ. Hospital MAS, Malmoe (Sweden). Dept. of Endocrinology

    2004-12-01

    The present study was aimed at assessing differences between the Nordic countries, if any, in late mortality among five-year survivors of childhood cancer. All cases diagnosed before the age of 20 years, between 1960 and 1989, were collected from all Nordic cancer registries. In total, 13,689 patients were identified as five-year survivors and during the extended follow-up 12.3% of them died. Mortality was analysed by decade of diagnosis, for all sites, and for leukaemia, Hodgkin's lymphoma, and central nervous system tumours separately. Analyses were done within a Cox proportional hazards regression framework with adjustments made for gender and age at diagnosis. Hazard ratios were calculated in relation to a weighted Nordic mean based on the proportion of five-year survivors in each country. Overall late mortality was significantly higher in Denmark and Finland than in Norway and Sweden. This could not be explained by inverse differences in five-year survival. The differences diminished over time and had disappeared in the last period. The pattern was similar for both genders. The disappearance of the differences was most probably the effect of a closer collaboration between Nordic paediatric oncologists with development and implementation of common protocols for treatment of childhood cancers in all countries.

  6. Case report: hydroquinone and/or glutaraldehyde induced acute myeloid leukaemia?

    Directory of Open Access Journals (Sweden)

    Alexopoulos Evangelos C

    2006-07-01

    Full Text Available Abstract Background Exposures to high doses of irradiation, to chemotherapy, benzene, petroleum products, paints, embalming fluids, ethylene oxide, herbicides, pesticides, and smoking have been associated with an increased risk of acute myelogenous leukemia (AML. Although there in no epidemiological evidence of relation between X-ray developer, fixer and replenisher liquids and AML, these included glutaraldehyde which has weakly associated with lymphocytic leukemia in rats and hydroquinone has been increasingly implicated in producing leukemia, causing DNA and chromosomal damage, inhibits topo-isomerase II, alter hematopoiesis and inhibit apoptosis of neoplastic cells. Case presentation Two white females (A and B hired in 1985 as medical radiation technologists in a primary care center, in Greece. In July 2001, woman A, 38-years-old, was diagnosed as having acute monocytic leukaemia (FAB M5. The patient did not respond to therapy and died threeweeks later. In August 2001, woman B, 35-year-old, was diagnosed with acute promyelocytic leukaemia (FAB M3. Since discharge, she is in continuous complete remission. Both women were non smokers without any medical history. Shortly after these incidents official inspectors and experts inspected workplace, examined equipment, archives of repairs, notes, interviewed and monitored employees. They concluded that shielding was inadequate for balcony's door but personal monitoring did not show any exceeding of TLV of 20 mSv yearly and cytogenetics analysis did not reveal findings considered to be characteristics of ionizing exposure. Equipment for developing photos had a long list of repairs, mainly leakages of liquids and increases of temperature. On several occasions the floor has been flooded especially during 1987–1993 and 1997–2001. Inspection confirmed a complete lack of ventilation and many spoiled medical x-ray films. Employees reported that an "osmic" level was continuously evident and frequently

  7. Fallon drill sites and field data

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This memo contains a listing of the cone penetrometer and well site locations for Dodge Ranch and Peraldo areas and the field ground-water chemistry data collected...

  8. Early Childhood Caries

    Directory of Open Access Journals (Sweden)

    Yumiko Kawashita

    2011-01-01

    Full Text Available Dental caries is one of the most common childhood diseases, and people continue to be susceptible to it throughout their lives. Although dental caries can be arrested and potentially even reversed in its early stages, it is often not self-limiting and progresses without proper care until the tooth is destroyed. Early childhood caries (ECC is often complicated by inappropriate feeding practices and heavy infection with mutans streptococci. Such children should be targeted with a professional preventive program that includes oral hygiene instructions for mothers or caregivers, along with fluoride and diet counseling. However, these strategies alone are not sufficient to prevent dental caries in high-risk children; prevention of ECC also requires addressing the socioeconomic factors that face many families in which ECC is endemic. The aim of this paper is to systematically review information about ECC and to describe why many children are suffering from dental caries.

  9. Childhood Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    R Dayal

    2014-03-01

    Full Text Available Obstructive sleep apnea (OSA is a common condition in childhood and can result insevere complications if left untreated. It is showing a rising trend in India. A significantassociation with obesity has been observed; however, some children with enlargedtonsils and/or adenoids may even be underweight. The patient usually presents withsnoring and other respiratory problems like mouth breathing, choking and gaspingepisodes in night. Poor school performance and neurocognitive deficits have beenreported. Pulmonary hypertension and cor pulmonale are seen in severe cases. Besidesthe history and clinical examination, for definitive diagnosis an overnightpolysomnographic evaluation is the gold standard. In all cases, the specific treatmentranges from simple lifestyle modifications and medications to surgeries likeadenotonsillectomy. Early diagnosis is vital.Key words: Childhood OSA, Obesity, adenotonsillar hypertrophy

  10. Genetics of Childhood Obesity

    Directory of Open Access Journals (Sweden)

    Jianhua Zhao

    2011-01-01

    Full Text Available Obesity is a major health problem and an immense economic burden on the health care systems both in the United States and the rest of the world. The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. Genome-wide association studies (GWAS have revealed strongly associated genomic variants associated with most common disorders; indeed there is general consensus on these findings from generally positive replication outcomes by independent groups. To date, there have been only a few GWAS-related reports for childhood obesity specifically, with studies primarily uncovering loci in the adult setting instead. It is clear that a number of loci previously reported from GWAS analyses of adult BMI and/or obesity also play a role in childhood obesity.

  11. Tibetan Nomad Childhood

    Directory of Open Access Journals (Sweden)

    Karma Dondrub

    2013-09-01

    Full Text Available A Tibetan Nomad Childhood by Kar+ma don 'grub. Kar+ma's life begins on the boundless Tibetan grassland in 1983 in Yushu (Yul shul Tibetan Autonomous Prefecture, Mtsho sgnon (Qinghai Province. Living in a black yak hair tent, Kar+ma begins tending his family's yak calves as soon as he can walk, in a grassland so barren that he is startled upon first seeing a tree at the age of eight. Charlatan livestock-stealing monks, anthrax, death, birth, happiness, and encounters with modern education create a powerful, unparalleled account of Tibetan nomad childhood in the late twentieth century - a way of life that will soon be forever gone.

  12. Brain Development in Childhood

    OpenAIRE

    Taki, Yasuyuki; Kawashima, Ryuta

    2012-01-01

    Although human brain development continues throughout childhood and adolescence, it is a non-linear process both structurally and functionally. Here we review studies of brain development in healthy children from the viewpoint of structure and the perfusion of gray and white matter. Gray matter volume increases and then decreases with age, with the developmental time of the peak volume differing among brain regions in the first and second decades of life. On the other hand, white matter volum...

  13. Early Childhood Development

    OpenAIRE

    Bakilana, Anne; Moucheraud, Corrina; McConnell, Christin; HASAN, Rifat

    2016-01-01

    Teenage pregnancies have potential negative consequences on the next generation. Children born to adolescent mothers are particularly at risk in terms of health, nutrition, cognitive and socio-emotional development. Evidence shows that the early years – especially the first 1,000 days – are crucially important for lifetime health, learning, and productivity. Particularly for the most vulnerable children and families, early childhood development (ECD) is a high return investment. This polic...

  14. Early Childhood Development

    OpenAIRE

    HASAN, Rifat; Moucheraud, Corrina; Bakilana, Anne; Nadeau, Sophie

    2015-01-01

    Teenage pregnancies have potential negative consequences on the next generation. Children born to adolescent mothers are particularly at risk in terms of health, nutrition, cognitive and socio-emotional development. Evidence shows that the early years – especially the first 1,000 days – are crucially important for lifetime health, learning, and productivity. Particularly for the most vulnerable children and families, early childhood development (ECD) is a high return investment. This polic...

  15. Conscientiousness: Origins in Childhood?

    OpenAIRE

    Eisenberg, Nancy; Duckworth, Angela L.; Spinrad, Tracy L.; Valiente, Carlos

    2012-01-01

    In this review, we evaluate developmental and personality research with the aim of determining if the personality trait of conscientiousness can be identified in children and adolescents. After concluding that conscientiousness does emerge in childhood, we discuss the developmental origins of conscientiousness with a specific focus on self-regulation, academic motivation, and internalized compliance/internalization of standards. Based on the accumulated body of evidence, we conclude that self...

  16. Childhood lymphoma in Yorkshire.

    OpenAIRE

    Davison, A. M.; McKinney, P A; Bailey, C C; Lewis, I.; Cartwright, R A; O'Brien, C.

    1992-01-01

    AIMS: A histopathological review of 43 cases of childhood non-Hodgkin's lymphoma (NHL) in an attempt to identify histological variables of prognostic importance. METHOD: Each case was reclassified according to the Working Formulation and an attempt made to allocate an immunophenotype using a panel of monoclonal antibodies. Results were correlated with clinical data on site and survival. RESULTS: Of the 43 cases, 30 were males and 13 females. There were 17 cases of lymphoblastic lymphoma, 15 c...

  17. Fatty liver in childhood

    OpenAIRE

    Ozturk,Yesim; Soylu, Ozlem Bekem

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is repor...

  18. Childhood ovarian malignancy.

    Science.gov (United States)

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-04-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4 and karyopherin-2 (KPNA2) have been helpful in differentiating ovarian yolk sac tumor from dysgerminoma, teratomas, and other pictures of hepatoid, endometrioid, clear cell carcinomatous, and adenocarcinomatous tissues with varied malignant potential. Before platinum therapy, these tumors were almost fatal in children. Fertility-conserving surgery with bleomycin, etoposide, and cisplatin has dramatically changed the survival rates in these patients. This modality gives cancer cure with healthy offspring to female patients with childhood ovarian tumor. Evidence also supports this protocol resulting in successful pregnancy rates and safety of cytotoxic drugs in children born to these patients. PMID:24757335

  19. Peer Bullying During Early Childhood

    OpenAIRE

    Hatice UYSAL; Çağlayan DİNÇER

    2012-01-01

    Peer bullying during early childhood is discussed along with the literature reviewed in this article with the purpose of drawing attention to peer bullying during early childhood and its significance, and contributing to studies which are few in number in Turkey. Peer bullying during early childhood was considered with its definition and types, people who play key roles in peer bullying, factors (gender, age, parents, and friendship) that relate to peer bullying, and what should be done befor...

  20. Stress and Obesity in Childhood

    OpenAIRE

    Koch, Felix-Sebastian

    2009-01-01

    Childhood obesity is a serious health problem and prevalence increases dramatically around the world, including Sweden. The aim of the current thesis was to examine parents’ and children’s stress in relation to childhood obesity. Parenting stress, social support, parental worries, and serious life events, as well as children’s temperament, self-esteem, body dissatisfaction, saliva cortisol, weight and height were measured to estimate stress and the relation between stress and childhood obesit...

  1. Psychiatric Aspects of Childhood Epilepsy

    OpenAIRE

    Pattanayak, Raman Deep; Sagar, Rajesh

    2012-01-01

    How to Cite this Article: Pattanayak RD, Sagar R. Psychiatric Aspects of Childhood Epilepsy. Iran J Child Neurol 2012;6(2):9-18.Childhood epilepsy is a chronic, recurrent disorder of unprovoked seizures. Theonset of epilepsy in childhood has significant implications for brain growth anddevelopment. Seizures may impair the ongoing neurodevelopmental processes and compromise the child’s intellectual and cognitive functioning, leading totremendous cognitive, behavioral and psychosocial consequen...

  2. Investigation of Childhood Abuse Experiences

    OpenAIRE

    AYDIN, Oktay

    2013-01-01

    In this study childhood abuse experiences between 18-25 years old males wasinvestigated according to some variables. The sample consist of 308 male. ChildhoodTrauma Questionnaire was applied to sample group to determine their childhood abuseexperiences. In addition to this, to determine some of demographical characteristics of thesubjects, a questionnaire was used. ANOVA and Pearson Moment Correlation CoefficentTechniques were used on the obtained results.At the and of the research;- People u...

  3. Childhood obesity and prevention approaches

    OpenAIRE

    Dilek Yildiz; Berna Eren Fidanci; Derya Suluhan

    2015-01-01

    Childhood obesity has increased dramatically during the past two decades. The growing incidence of childhood obesity is alarming, given the significant short and long term health problems associated with obesity. Being overweight or obese may increase the rate of non-communicable diseases such as type 2 diabetes and cardiovascular disease in adulthood. It may contribute to shortening life expectancy and adversely affects the quality of life. Therefore, it is important to prevent childhood obe...

  4. Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Nóra Kutszegi

    Full Text Available L-asparaginase (ASP is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL. However, hypersensitivity reactions (HSRs to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26; p = 4.70E-04, while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176 were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53; p = 8.48E-04 and OR = 3.02 (1.36-6.73; p = 6.76E-03, respectively. Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.

  5. 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.

  6. Specific cytotoxic T-cell immune responses against autoantigens recognized by chronic lymphocytic leukaemia cells.

    Science.gov (United States)

    Zaleska, Joanna; Skorka, Katarzyna; Zajac, Malgorzata; Karczmarczyk, Agnieszka; Karp, Marta; Tomczak, Waldemar; Hus, Marek; Wlasiuk, Paulina; Giannopoulos, Krzysztof

    2016-08-01

    Mounting evidence suggests that autoreactivity and inflammatory processes are involved in the pathogenesis of chronic lymphocytic leukaemia (CLL). Cytoskeletal proteins, including non-muscle myosin heavy chain IIA (MYHIIA), vimentin (VIM) and cofilin-1 (CFL1), exposed on the surface of apoptotic cells have been identified as autoantigens that are recognized by the specific B-cell receptors of the CLL cells. In 212 CLL patients analysed with quantitative reverse transcriptase-polymerase chain reaction we found CFL1 overexpression and low expression of MYH9 in comparison with healthy volunteers. We detected specific cytotoxic immune responses for peptides derived from MYHIIA in 66·7%, VIM in 87·5% and CFL1 in 62·5% CLL patients in an Enzyme-Linked ImmunoSpot assay. Low frequencies of autoreactive peptide-specific T cells were detected against MYHIIA, VIM and CFL1 in CLL patients ex vivo; most of the detected cells had an effector-memory phenotype. Our findings support the existence of cytotoxic immune responses against three autoantigens that have been identified as targets of CLL clonotypic B-cell receptors. The presence of autoreactive CD8(+) T cells against MYHIIA, VIM and CFL1 in CLL patients indicates the involvement of antigen-specific autoreactive T cells in the pathogenesis of CLL.

  7. Probability Prediction in Multistate Survival Models for Patients with Chronic Myeloid Leukaemia

    Institute of Scientific and Technical Information of China (English)

    FANG Ya; Hein Putter

    2005-01-01

    In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis.After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse,especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or afterrelapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.

  8. The possible role of radiotherapy in chronic lymphocytic leukaemia: a critical review

    International Nuclear Information System (INIS)

    The few clinical studies which have utilized irradiation as a treatment modality for chronic lymphocytic leukaemia (CLL) during the last two decades have led to rather conflicting and sometimes disappointing results. Because new data are emerging (stratification of CLL in various subgroups, better understanding of the role of the normal T-cell subsets, better knowledge of the interaction between irradiation and haematopoiesis, and of the radiosensitivity of the various lymphocyte subpopulations), one can reconsider the possible role radiotherapy, particularly splenic irradiation, can play as an alternative treatment to chemotherapy for CLL. Haematological toxicity is still limiting the use of TBI. The spleen irradiation avoids this drawback. Recent data suggest that this splenic irradiation could be efficient by means of several mechanisms; the successive destruction, fraction after fraction, of the part of the malignant lymphocyte clone present in the spleen is likely to be the main therapeutic explanation, with the knowledge that the lower the differentiation of the malignant clone, the more efficacious the irradiation. But in parallel, the destruction of the large subset of T-suppressors which is constantly present in the spleen may account for the improvement of the peripheral blood count after splenic irradiation, and possibly for a direct effect towards the malignant clone. With respect to these new data, splenic irradiation clearly needs further clinical evaluation in the treatment of CLL. (Auth.)

  9. Caveolin-1 interacts with the Gag precursor of murine leukaemia virus and modulates virus production

    Directory of Open Access Journals (Sweden)

    Koester Mario

    2006-09-01

    Full Text Available Abstract Background Retroviral Gag determines virus assembly at the plasma membrane and the formation of virus-like particles in intracellular multivesicular bodies. Thereby, retroviruses exploit by interaction with cellular partners the cellular machineries for vesicular transport in various ways. Results The retroviral Gag precursor protein drives assembly of murine leukaemia viruses (MLV at the plasma membrane (PM and the formation of virus like particles in multivesicular bodies (MVBs. In our study we show that caveolin-1 (Cav-1, a multifunctional membrane-associated protein, co-localizes with Gag in a punctate pattern at the PM of infected NIH 3T3 cells. We provide evidence that Cav-1 interacts with the matrix protein (MA of the Gag precursor. This interaction is mediated by a Cav-1 binding domain (CBD within the N-terminus of MA. Interestingly, the CBD motif identified within MA is highly conserved among most other γ-retroviruses. Furthermore, Cav-1 is incorporated into MLV released from NIH 3T3 cells. Overexpression of a GFP fusion protein containing the putative CBD of the retroviral MA resulted in a considerable decrease in production of infectious retrovirus. Moreover, expression of a dominant-negative Cav-1 mutant affected retroviral titres significantly. Conclusion This study demonstrates that Cav-1 interacts with MLV Gag, co-localizes with Gag at the PM and affects the production of infectious virus. The results strongly suggest a role for Cav-1 in the process of virus assembly.

  10. The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Eswaran, J; Sinclair, P; Heidenreich, O; Irving, J; Russell, L J; Hall, A; Calado, D P; Harrison, C J; Vormoor, J

    2015-08-01

    The B-cell receptor (BCR) and its immature form, the precursor-BCR (pre-BCR), have a central role in the control of B-cell development, which is dependent on a sequence of cell-fate decisions at specific antigen-independent checkpoints. Pre-BCR expression provides the first checkpoint, which controls differentiation of pre-B to immature B-cells in normal haemopoiesis. Pre-BCR signalling regulates and co-ordinates diverse processes within the pre-B cell, including clonal selection, proliferation and subsequent maturation. In B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), B-cell development is arrested at this checkpoint. Moreover, malignant blasts avoid clonal extinction by hijacking pre-BCR signalling in favour of the development of BCP-ALL. Here, we discuss three mechanisms that occur in different subtypes of BCP-ALL: (i) blocking pre-BCR expression; (ii) activating pre-BCR-mediated pro-survival and pro-proliferative signalling, while inhibiting cell cycle arrest and maturation; and (iii) bypassing the pre-BCR checkpoint and activating pro-survival signalling through pre-BCR independent alternative mechanisms. A complete understanding of the BCP-ALL-specific signalling networks will highlight their application in BCP-ALL therapy.

  11. [Cytotoxicity of polyphenolic/flavonoid compounds in a leukaemia cell culture].

    Science.gov (United States)

    Josipović, Pavle; Orsolić, Nada

    2008-12-01

    Flavonoid components of propolis are biologically active substances with antioxidative, immunostimulative, immunomodulative, and anti-inflamatory properties. The aim of the study was to investigate their cytotoxic effect on different leukaemia cell lines. For this purpose we used five different flavonoids (quercetin, caffeic acid, chrysin, naringenin, and naringin) and five types of leukemia cell lines (MOLT, JURKAT, HL-60, RAJI and U937). Cells were cultured at 37 degrees C in the RPMI-1640 medium supplemented with 10% FCS in humified atmosphere with 5% of CO2. Flavonoids were added in the following concentrations: 100 microg mL(-1), 50 microg mL(-1), 25 microg mL(-1), or 12.5 microg mL(-1). The results show different dose- and cell-type-dependent cytotoxicity. Among the flavonoids, quercetin showed the strongest cytotoxic effect in all cell lines. Caffeic acid and chrisyn also expressed a high level of cytotoxicty. Treatment of U937 and HL-60 cell lines with low concentrations of chrisyn or naringenin stimulated cell proliferation. These results suggest a biphase effect of the tested compounds on monocyte cell lines. Cytotoxicity and growth stimulation mechanisms caused directly by flavonoids should further be investigated on the molecular level.

  12. An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images

    Science.gov (United States)

    Chin Neoh, Siew; Srisukkham, Worawut; Zhang, Li; Todryk, Stephen; Greystoke, Brigit; Peng Lim, Chee; Alamgir Hossain, Mohammed; Aslam, Nauman

    2015-10-01

    This research proposes an intelligent decision support system for acute lymphoblastic leukaemia diagnosis from microscopic blood images. A novel clustering algorithm with stimulating discriminant measures (SDM) of both within- and between-cluster scatter variances is proposed to produce robust segmentation of nucleus and cytoplasm of lymphocytes/lymphoblasts. Specifically, the proposed between-cluster evaluation is formulated based on the trade-off of several between-cluster measures of well-known feature extraction methods. The SDM measures are used in conjuction with Genetic Algorithm for clustering nucleus, cytoplasm, and background regions. Subsequently, a total of eighty features consisting of shape, texture, and colour information of the nucleus and cytoplasm sub-images are extracted. A number of classifiers (multi-layer perceptron, Support Vector Machine (SVM) and Dempster-Shafer ensemble) are employed for lymphocyte/lymphoblast classification. Evaluated with the ALL-IDB2 database, the proposed SDM-based clustering overcomes the shortcomings of Fuzzy C-means which focuses purely on within-cluster scatter variance. It also outperforms Linear Discriminant Analysis and Fuzzy Compactness and Separation for nucleus-cytoplasm separation. The overall system achieves superior recognition rates of 96.72% and 96.67% accuracies using bootstrapping and 10-fold cross validation with Dempster-Shafer and SVM, respectively. The results also compare favourably with those reported in the literature, indicating the usefulness of the proposed SDM-based clustering method.

  13. A neutron study of the feline leukaemia virus fusion peptide: Implications for biological fusion?

    Science.gov (United States)

    Davies, Sarah M. A.; Darkes, Malcolm J. M.; Bradshaw, Jeremy P.

    Neutron diffraction studies were performed on stacked phospholipid bilayers to determine the effects of the feline leukaemia virus (FeLV) fusion peptide on membrane structure. Bilayers were composed of dioleoylphosphatidylcholine with 50% (mol) dioleoylphosphatidylglycerol. Neutron scattering profiles with peptide present showed an increase in scattering density in the lipid-tails region, whilst scattering by the lipid headgroup region was decreased. This is interpreted as a lowering of the packing density of the lipid headgroups and an increase in the packing density of the lipid tails. Modelling studies and experimental evidence have suggested that fusion peptides catalyse fusion by increasing the negative curvature of the target membrane's outer monolayer. Our results presented here add support to this hypothesis for the fusion mechanism. The 2H 2O scattering profile was also slightly perturbed in the lipid headgroup region with 1% (mol)FeLV fusion peptide present. The FeLV peptide had no significant effect on the organisation of bilayers containing only dioleoylphosphatidylcholine.

  14. A high rate of telomeric sister chromatid exchange occurs in chronic lymphocytic leukaemia B-cells.

    Science.gov (United States)

    Medves, Sandrine; Auchter, Morgan; Chambeau, Laetitia; Gazzo, Sophie; Poncet, Delphine; Grangier, Blandine; Verney, Aurélie; Moussay, Etienne; Ammerlaan, Wim; Brisou, Gabriel; Morjani, Hamid; Géli, Vincent; Palissot, Valérie; Berchem, Guy; Salles, Gilles; Wenner, Thomas

    2016-07-01

    Cancer cells protect their telomere ends from erosion through reactivation of telomerase or by using the Alternative Lengthening of Telomere (ALT) mechanism that depends on homologous recombination. Chronic lymphocytic leukaemia (CLL) B cells are characterized by almost no telomerase activity, shelterin deregulation and telomere fusions. To characterize telomeric maintenance mechanisms in B-CLL patients, we measured their telomere length, telomerase expression and the main hallmarks of the ALT activity i.e. C-circle concentration, an extra-chromosomal telomere repeat (ECTR), and the level of telomeric sister chromatid exchange (T-SCE) rate. Patients showed relative homogenous telomere length although almost no TERT transcript and nearly no C-circle were evidenced. Nevertheless, compared with normal B cells, B-CLL cells showed an increase in T-SCE rate that was correlated with a strong down-regulation of the topoisomerase III alpha (TOP3A) expression, involved in the dissolution of Holliday Junctions (HJ), together with an increased expression of SLX1A, SLX4, MUS81 and GEN1, involved in the resolution of HJ. Altogether, our results suggest that the telomere maintenance mechanism of B-CLL cells do not preferentially use telomerase or ALT. Rather, the rupture of the dissolvasome/resolvasome balance may increase telomere shuffling that could homogenize telomere length, slowing telomere erosion in this disease. PMID:26970083

  15. Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Hakim, I; Rechavi, G; Brok-Simoni, F; Grossman, Z; Amariglio, N; Mandel, M; Ramot, B; Ben-Bassat, I; Katzir, N

    1993-07-01

    Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and C mu gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.

  16. Noma in a child with acute leukaemia: when the 'face of poverty' finds an ally.

    Science.gov (United States)

    Singh, Amitabh; Mandal, Anirban; Seth, Rachna; Kabra, Sushil Kumar

    2016-01-06

    A 2-year-6-month old, appropriately immunised, well-thriving boy, symptomatic for the past 6 months, presented with recurrent fever, progressive pallor, lymphadenopathy and a raw area on the right cheek, with discharging sinus. The necrotising infection of the face developed after one and half months of febrile illness. This febrile illness with bicytopaenia was diagnosed as enteric fever and treated with antibiotics. Skin grafting was performed for the full-thickness defect of the face. The patient continued to have a non-healing oral ulcer with progressive pallor and was finally diagnosed as having acute lymphoblastic leukaemia. Immunodeficiency was ruled out by appropriate investigations. Noma is an indirect measure of extreme poverty, but malignancy is known to predispose to this debilitating condition. The worldwide incidence of Noma is reported to be 30,000-140,000, with a preponderance in sub-Saharan Africa. This case emphasises the need for a thorough search for the underlying illness predisposing to a rare opportunistic infection such as Noma in a well-thriving child.

  17. Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study

    DEFF Research Database (Denmark)

    Villumsen, Marie; Sørup, Signe; Jess, Tine;

    2009-01-01

    Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines...... cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.......31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas....

  18. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia

    International Nuclear Information System (INIS)

    We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY-TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogenic (BMT)), diagnosis (acute lymphoblast leukaemia (ALL) ora cute myeloid leukaemia (AML)), status (early first complete remission, CR-1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI. (author)

  19. The influence of 2- chlorodeoxyadenosine in combination with tumour necrosis factor-α or its mutein on murine leukaemias L1210 and P388

    Directory of Open Access Journals (Sweden)

    J. Góra-Tybor

    1995-01-01

    Full Text Available We investigated the influence of 2-chlorodeoxyadenosine (2-CdA in combination with tumour necrosis factor-α (TNFα or its mutein VI, which differs from the native molecule by N-terminal amino acid composition, on the survival time of mice inoculated with leukaemia L1210 or P388. Groups of mice with leukaemia L1210 and P388 receiving 2-CdA combined with TNFα had shorter survival times than animals treated with these agents separately. In contrast, the administration of 2-CdA in conjunction with mutein VI, prolonged the survival of mice inoculated with these leukaemias as compared with animals receiving these agents separately. The results of the present study emphasize the importance of the biological activity of the TNFα molecule N-terminus.

  20. Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias

    Energy Technology Data Exchange (ETDEWEB)

    Bouchet, Sandrine; Bauvois, Brigitte, E-mail: brigitte.bauvois@crc.jussieu.fr [INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris 75006 (France)

    2014-04-04

    Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  1. Adverse Childhood Experiences and Childhood Autobiographical Memory Disturbance

    Science.gov (United States)

    Brown, David W.; Anda, Robert F.; Edwards, Valerie J.; Felitti, Vincent J.; Dube, Shanta R.; Giles, Wayne H.

    2007-01-01

    Objective: To examine relationships between childhood autobiographical memory disturbance (CAMD) and adverse childhood experiences (ACEs) which are defined as common forms of child maltreatment and related traumatic stressors. Methods: We use the ACE score (an integer count of eight different categories of ACEs) as a measure of cumulative exposure…

  2. Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    W. Y. Lim

    2015-01-01

    Full Text Available Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

  3. Adverse Childhood Experiences and Hallucinations

    Science.gov (United States)

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  4. Teachers in Early Childhood Policy

    Science.gov (United States)

    Kilderry, Anna

    2014-01-01

    This paper examines teacher accountability and authority in early childhood policy. It reports on data from a study that investigated the influences affecting early childhood teacher decision-making at the preschool level in Victoria, Australia. Using a question raised by Ball "Where are the teachers in all this [policy]?" provided a…

  5. Markets and Childhood Obesity Policy

    Science.gov (United States)

    Cawley, John

    2006-01-01

    In examining the childhood obesity epidemic from the perspective of economics, John Cawley looks at both possible causes and possible policy solutions that work through markets. The operation of markets, says Cawley, has contributed to the recent increase in childhood overweight in three main ways. First, the real price of food fell. In…

  6. Early Childhood Inclusion in Spain

    Science.gov (United States)

    Giné, Climent; Balcells-Balcells, Anna; Cañadas, Margarita; Paniagua, Gema

    2016-01-01

    This article describes early childhood inclusion in educational settings in Spain. First, we address the legislative framework of preschool education in Spain and offer a brief analysis of some relevant issues, including the current situation of early childhood education and inclusion at this stage. Second, current policies and practices relating…

  7. Combined dyslipidemia in childhood.

    Science.gov (United States)

    Kavey, Rae-Ellen W

    2015-01-01

    Combined dyslipidemia (CD) is now the predominant dyslipidemic pattern in childhood, characterized by moderate-to-severe elevation in triglycerides and non-high-density lipoprotein cholesterol (non-HDL-C), minimal elevation in low-density lipoprotein cholesterol (LDL-C), and reduced HDL-C. Nuclear magnetic resonance spectroscopy shows that the CD pattern is represented at the lipid subpopulation level as an increase in small, dense LDL and in overall LDL particle number plus a reduction in total HDL-C and large HDL particles, a highly atherogenic pattern. In youth, CD occurs almost exclusively with obesity and is highly prevalent, seen in more than 40% of obese adolescents. CD in childhood predicts pathologic evidence of atherosclerosis and vascular dysfunction in adolescence and young adulthood, and early clinical cardiovascular events in adult life. There is a tight connection between CD, visceral adiposity, insulin resistance, nonalcoholic fatty liver disease, and the metabolic syndrome, suggesting an integrated pathophysiological response to excessive weight gain. Weight loss, changes in dietary composition, and increases in physical activity have all been shown to improve CD significantly in children and adolescents in short-term studies. Most importantly, even small amounts of weight loss are associated with significant decreases in triglyceride levels and increases in HDL-C levels with improvement in lipid subpopulations. Diet change focused on limitation of simple carbohydrate intake with specific elimination of all sugar-sweetened beverages is very effective. Evidence-based recommendations for initiating diet and activity change are provided. Rarely, drug therapy is needed, and the evidence for drug treatment of CD in childhood is reviewed. PMID:26343211

  8. CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

    Science.gov (United States)

    Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor

    2011-07-01

    Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with ~ 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of ~ 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in ~ 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of ~ 12 nm retained bright fluorescence over an extended duration of ~ a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of ~ 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of ~ 8.2% in human peripheral blood cells (PBMCs) which are CD33low. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

  9. CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor, E-mail: manzoork@aims.amrita.edu, E-mail: ullasmony@aims.amrita.edu [Amrita Centre for Nanoscience and Molecular Medicine, Amrita Institute of Medical Science, Cochin 682 041 (India)

    2011-07-15

    Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with {approx} 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of {approx} 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in {approx} 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of {approx} 12 nm retained bright fluorescence over an extended duration of {approx} a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of {approx} 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of {approx} 8.2% in human peripheral blood cells (PBMCs) which are CD33{sup low}. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

  10. Research of the Relationship between CSC and Leukaemia%CSC与白血病相关研究

    Institute of Scientific and Technical Information of China (English)

    吴伟

    2011-01-01

    白血病是导致人类死亡的主要因素之一.尽管在白血病治疗方面取得了巨大进展,但是其较高的复发率还是会导致死亡.肿瘤干细胞(CSC)假说认为,CSC具有自我更新能力、无限增殖和肿瘤形成能力.CSC已在急性粒细胞白血病等血液系疾病中得到证实.CSC研究包括CSC分离鉴定、探索调控机制以及临床肿瘤治疗等方面.分析近年来CSC在白血病领域中的主要研究成果,为血液系肿瘤治疗和CSC的深层研究提供思路.%Leukaemia is one of the leading causes of human death. While great progress has been made in leukaemia treatment, its high recurrence rate still leads to death. Cancer stem cells( CSC )hypothesis thinks that there is some cancer tissue with self-renewal ability, unlimited proliferation and tumor-forming ability.CSC has been confirmed in acute myelocytic leukemia and other hematological malignancy. Efforts were dedicated to such topics including:identification of CSC, exploration of the regulatory mechanism of CSC, treatment of clinical oncology,etc. Here is to analyze the advances of CSC with leukaemia in recent years,and to propose a prospect for hematological malignancy therapy and deeper CSC research.

  11. Acute myeloid leukaemia induced by mitoxantrone: case report Leucemia mielóide aguda induzida por mitoxantrone: relato de caso

    Directory of Open Access Journals (Sweden)

    Walter Oleschko Arruda

    2005-06-01

    Full Text Available Mitoxantrone (MX is an immunosupressant drug used in secondarily progressive multiple sclerosis (SPMS and in relapsing-remitting multiple sclerosis (RRMS. It has a leukemogenesis potential induced by cytogenetic abnormalities, though with a low incidence. Promyelocitic leukaemia (type M3 and other forms of acute myeloblastic leukaemias (M4 and M5 have been described in a few MS patients who received MX during their treatment. We describe a white female patient, 47 year-old, with SPMS (EDSS = 4 with 14 years of disease. She received MX during her disease and developed acute promyelocytic leukaemia (M3, with severe thrombocytopenia 30 months later. She ultimately died due to intracerebral hemorrhage. Other cases of treatment related to AML are reviewed and discussed.Mitoxantrone (MX é uma agente imunossupressor utilizado nas formas progressivas secundárias de esclerose múltipla (EM ou formas surto-remissão sem resposta com outras formas de tratamento (p.ex. beta-interferon, acetato de glatirâmer. Com o uso desta medicação, ocorre uma incidência maior, embora pequena, de desenvolvimento de leucemia mielóide aguda induzida por quimioterápicos. Descrevemos o caso de uma paciente com forma progressiva secundária de EM, submetida a uma dose única de MX de 15mg e que 30 meses após desenvolveu quadro fulminante de leucemia promieloblástica aguda (M3, com trombocitopenia grave. A paciente faleceu por hemorragia intracerebral maciça. É feita revisão de outros casos relatados na literatura e os possíveis mecanismos de desenvolvimento desta complicação grave secundária ao uso do MX.

  12. Subclinical hypothyroidism in childhood.

    LENUS (Irish Health Repository)

    O'Grady, M J

    2012-02-01

    Subclinical hypothyroidism (SH) is defined as an elevated thyroid stimulating hormone (TSH) in association with a normal total or free thyroxine (T4) or triiodothyronine (T3). It is frequently encountered in both neonatology and general paediatric practice; however, its clinical significance is widely debated. Currently there is no broad consensus on the investigation and treatment of these patients; specifically who to treat and what cut-off level of TSH should be used. This paper reviews the available evidence regarding investigation, treatments and outcomes reported for childhood SH.

  13. Increasing Childhood Influenza Vaccination

    Science.gov (United States)

    Nowalk, Mary Patricia; Lin, Chyongchiou J.; Hannibal, Kristin; Reis, Evelyn C.; Gallik, Gregory; Moehling, Krissy K.; Huang, Hsin-Hui; Allred, Norma J.; Wolfson, David H.; Zimmerman, Richard K.

    2014-01-01

    Background Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. Purpose To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. Methods In 2011–2012, 20 primary care practices treating children were randomly assigned to Intervention and Control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. Results The average vaccination differences from pre-intervention to the intervention year were significantly larger in the Intervention arm (n=10 practices) than the Control arm (n=10 practices), for children aged 2–8 years (10.2 percentage points (pct pts) Intervention vs 3.6 pct pts Control) and 9–18 years (11.1 pct pts Intervention vs 4.3 pct pts Control, p<0.05), for non-white children (16.7 pct pts Intervention vs 4.6 pct pts Control, p<0.001), and overall (9.9 pct pts Intervention vs 4.2 pct pts Control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race and intervention, the likelihood of vaccination increased with younger age group (6–23 months), white race, commercial insurance, the practice’s pre-intervention vaccination rate, and being in the Intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9–18 years. Conclusions A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza

  14. Stroke in childhood

    OpenAIRE

    Serap Teber; Gülhis Deda

    2011-01-01

    Stroke in childhood is one of the most common causes of death or severe impairment worldwide, with annual incidence estimated from 1,3 to 13 cases/100.000 population. The definition of stroke consists both of arterial ischemic stroke (AIS) and hemorrhagic stroke. The incidence of ischemic and hemorrhagic stroke in children is approximately the same, in contrast to adults, while the incidence is higher in boys than it is in girls. Risks factors for pediatric stroke differ from those for adults...

  15. Migraine and lifestyle in childhood.

    Science.gov (United States)

    Casucci, Gerardo; Villani, Veronica; d'Onofrio, Florindo; Russo, Antonio

    2015-05-01

    Migraine is one of the most frequently reported somatic complaints in childhood, with a negative impact on health-related quality of life. The incidence of migraine in childhood has substantially increased over the past 30 years, probably due to both increased awareness of the disease and lifestyle changes in this age group. Indeed, several conditions have been identified as risk factors for migraine in childhood. Amongst these, dysfunctional family situation, the regular consumption of alcohol, caffeine ingestion, low level of physical activity, physical or emotional abuse, bullying by peers, unfair treatment in school and insufficient leisure time seem to play a critical role. Nevertheless, there are only few studies about the association between migraine and lifestyle in childhood, due to previous observations specifically focused on "headache" in children. In this brief review, we will concentrate upon recent studies aimed to explore migraine and lifestyle risk factors in childhood. PMID:26017522

  16. New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22)(q34;p11;q11)

    OpenAIRE

    Abdeljabar El Andaloussi; Chrystele Bilhou-Nabera

    2007-01-01

    A Chronic myeloid leukaemia (CML) case with a new complex t(9;18;22)(q34;p11;q11) of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH). In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importa...

  17. New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22(q34;p11;q11

    Directory of Open Access Journals (Sweden)

    Abdeljabar El Andaloussi

    2007-01-01

    Full Text Available A Chronic myeloid leukaemia (CML case with a new complex t(9;18;22(q34;p11;q11 of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH. In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importance of combined cytogenetic analysis for diagnosis and guidance of treatment in clinical diagnosis of CML.

  18. A 14-year paraneoplastic rash: urticarial vasculitis and dermal binding bullous pemphigoid secondary to chronic lymphocytic leukaemia.

    Science.gov (United States)

    Kassim, J M; Igali, L; Levell, N J

    2015-06-01

    A 72-year-old woman with a 14-year history of urticarial vasculitis (UV) and a 13-year history of bullous pemphigoid (BP) presented with associated progressive chronic lymphocytic leukaemia (CLL). Both skin conditions responded poorly to treatment, until chemotherapy for CLL was commenced. The skin features showed a clear paraneoplastic course, resolving with chemotherapy and recurring when the CLL relapsed and the lymphocyte count rose above 5 × 10(9)/L. No case of UV secondary to CLL, and very few cases of BP related to CLL have been reported, and no paraneoplastic rash of any type lasting 14 years has been reported previously. PMID:25524180

  19. Clofarabine and high-dose cytosine arabinoside in the treatment of refractory or relapsed acute myeloid leukaemia

    OpenAIRE

    Tse, Eric; Anskar Y. H. Leung; Sim, Joycelyn; Lee, Harold K.K.; Liu, Herman S. Y.; Yip, Sze-Fai; Kwong, Yok-Lam

    2011-01-01

    Clofarabine (40 mg/m 2/day×5) and high-dose cytosine arabinoside (Ara-C, 1-2 g/m 2/day×5) were used in 10 men and 11 women, at a median age of 45 (22-62) years, with refractory (N=4) and relapsed (N=17) acute myeloid leukaemia, after a median of 3 (2-5) prior regimens. Grade 4 myelosuppression was observed in all cases, with two patients dying of bacterial sepsis. Nine patients achieved a complete remission. Disease status, number of prior therapies, and cytogenetic aberrations were not assoc...

  20. Alternating hemiparesis and orolingual apraxia as manifestations of methotrexate neurotoxicity in a paediatric case of acute lymphoblastic leukaemia.

    Science.gov (United States)

    Yap, Siew Mei; MacEneaney, Peter; Ryan, Clodagh; O'Toole, Orna

    2016-01-01

    A 15-year-old girl with a recent diagnosis of acute lymphoblastic leukaemia was admitted to hospital with pancytopaenia after having received high-dose intrathecal methotrexate 1 day prior. During the next week she had intermittent episodes of alternating hemiparesis associated with speech arrest lasting minutes to hours at a time. The episodes were not associated with altered level of consciousness or headache. MRI of the brain showed features consistent with methotrexate encephalopathy. This report discusses the typical clinical and radiological features of methotrexate neurotoxicity in addition to differential diagnoses and the proposed pathophysiological mechanisms. PMID:27113788

  1. Nonfatal suicidal behavior among women prisoners: the predictive roles of childhood victimization, childhood neglect, and childhood positive support.

    Science.gov (United States)

    Tripodi, Stephen J; Onifade, Eyitayo; Pettus-Davis, Carrie

    2014-04-01

    Women entering prison report high rates of childhood victimization. Women in prison also report higher rates of nonfatal suicidal behavior (self-reported suicide attempts) than women in the general population and similar rates to their male counterparts despite having significantly lower suicide rates than males in the general population. Yet, there is a dearth of research that addresses the relationship between childhood victimization and suicidality for women prisoners in the United States. The purpose of this study is (a) to assess the relationship between childhood victimization and nonfatal suicidal behavior for a random sample of women prisoners; (b) to investigate predictive differences between childhood physical victimization, childhood sexual victimization, childhood neglect, and childhood support; and (c) to determine whether women prisoners with higher frequencies of childhood victimization and neglect are more likely to have attempted suicide than women prisoners with lower frequencies. Results indicate that childhood victimization, neglect, and lack of support are all significantly associated with nonfatal suicidal behavior among women prisoners. Frequency of childhood neglect had a larger effect size than frequency of childhood physical victimization, childhood sexual victimization, and lack of support. The results of this study add to the growing body of literature on childhood victimization and suicidality in general, and nonfatal suicidal behavior for prisoner populations in particular. The article ends with a discussion on clinical implications; particularly the finding that frequency of childhood victimization, childhood neglect, and lack of childhood support matters when determining the risk of suicidality. PMID:23315427

  2. Tritiated Thymidine as Tracer in DNA Metabolism and Cell Dynamics of Experimental Myeloid Leukaemia

    International Nuclear Information System (INIS)

    Tritium has been used as an isotopic tracer in a variety of biological problems in Israel. We wish to report, in particular, some findings in which tritiated thymidine (TH3) has been used to follow the cell dynamics in experimental myeloid leukaemia and also to investigate the mechanism of its incorporation into the DNA of these and Ehrlich ascites tumour cells. The leukaemic cells were labelled in-vivo by injecting the TH3 into the jugular vein. The dose was 1 pc/g/rat. The rate of appearance of the labelled cells in the peripheral blood and in the ascitic tumour of the animal, was estimated. In other experiments the rate of the dilution of the label in the nuclei was evaluated and thus it was possible to estimate the cellular doubling time in the myelocyte population. The dynamics of transfused leukaemia cells were investigated by injecting labelled myelocytes into the jugular vein of normal and leukaemic rats. Their rate of disappearance from the blood was measured. Various organs were examined for the labelled cells and it was found that soon after injection the cells were mainly trapped by the lungs, later by the spleen and to a lesser extent by the liver. After 24 h no labelled cells were detectable in any of the organs. Information was thus obtained on the fate of the leukaemic myelocytes in various organs of the normal and leukaemic animals. In in-vitro experiments, TH3 was added to the cell suspension in a concentration of 1 p.c/ml. In the course of the in-vitro labelling it was observed that the number of labelled cells was 40 times higher than the number of mitoses. (The same was found also after administering the TH3 in-vivo.) The rate of incorporation of the TH3 was established. Concentrations between 0.0036 p mole x 103 and 1.8 μmolex 10-3 were tested. It was found that the per cent of cells incorporating the label is constant for the various concentrations of thymidine. The number of grains per nucleus increased with the increase of the

  3. Acute hemiplegia in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Okuno, Takehiko; Takao, Tatsuo; Itoh, Masatoshi; Konishi, Yukuo; Nakano, Shozo (Kyoto Univ. (Japan). Faculty of Medicine)

    1983-04-01

    The results of CT in 100 patients with acute hemiplegia in childhood are reported here. The etiology was various: 2 patients had infratentorial brain tumors, 56 had cerebral vascular diseases, 3 had head injuries, 16 had intracranial infectious diseases, one had postinfectious encephalomyelitis, one had multiple sclerosis, 2 had epilepsy, and the diagnosis of 19 were unknown. Eleven patients had a normal CT and a good prognosis. As for the type of onset, there were patients of type 1 with fever and 42 with convulsions and unconsciousness; those of type 2 with convulsions and unconsciousness were 12, and those of type 3 without fever and convulsions were 46. This classification is assumed to be useful, as the type of onset is characteristic of the etiology. Six patients were diagnosed correctly by repeated examinations, although the first CT did not reveal any remarkable findings. Capsular infarction, occlusion of the posterior cerebral artery in acute hemiplegia in childhood, abnormal findings of the internal capsule, thalamus, and midbrain in a patient with postinfectious encephalomyelitis, and a diffuse low density in the CT of the unilateral hemisphere in the patients with acute encephalopathy and acute hemiplegia of an obscure origin have been found after the introduction of computerized tomography.

  4. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients

    Institute of Scientific and Technical Information of China (English)

    JYShi; ZZZhang; SJZhu; YMGu; BWLi; GBai; XTGao; XDHu; JJin; WHuang; WChen; ZChen

    2005-01-01

    Development of resistance to 1-beta-arabinofuranosylcytosine (AraC) is a major obstacle in the treatment of patients with acute myeloid leukaemia (AML). Deficiency of functional deoxycytidine kinase (dCK) plays an important role in AraC resistance in vitro. We screened 5378 bp sequences of the dCK gene, including all exons and the 5' flanking region, and identified two single nucleotide polymorphisms (SNPs) in the regulatory region (rSNPs) with high allele frequencies. These two rSNPs (-201 C>T and -360C>G) formed two major haplotypes. Genotyping with sequencing and MassARRAY system among 122 AML patients showed that those with -360CG/-201CT and -360GG/-201TT compound genotypes (n = 41) displayed a favourable response to chemotherapy whereas those with -360CC/-201CC (n= 81) tended to have a poor response (P = 0.025). Moreover, real-time quantitative reverse transcriptase-polymerase chain reaction showed that patients with -360CG/-201CT and -360GG/-201TT genotypes expressed higher level of dCK mRNA compared to those with the -360CC/-201CC genotype (P = 0.0034). Luciferase-reporter assay showed that dCK 5' regulatory region bearing -360G/-201T genotype alone had an eight-fold greater transcriptional activation activity compared to that with -360C/-201C genotype, whereas co-transfection of both -360G/-201T and -360C/-201C constructs mimicked the heterozygous genotype, which exhibited a four-fold greater activity compared to that with -360C/-201C. These results indicate that rSNP haplotypes of dCK gene may serve as a genetic marker for predicting drug responsiveness, which will be beneficial in establishing more effective AML chemotherapeutic regimens.

  5. Survivin Antisense Oligodeoxy-Nucleotid Induces Apoptosis in Leukaemia Cell Line K562

    Institute of Scientific and Technical Information of China (English)

    Lijun Chen; Qiuyue Jin; Hong Xie; Ruimin Wang; Li Yao

    2006-01-01

    OBJECTIVE To investigate the effects of survivin antisense oligodeoxynucleotid (ASODN) on proliferation and apoptosis in the chronic myeloid leukemia cell line K562.METHODS Different concentrations of an antisense oligodeoxy-nucleotid and control sequence (scrambled ODN) targeting the survivin gene were transferred into K562 by a lipofectin reagent. The MTT assay was used to measure the growth inhibitory rate, IC50, and to observe the cytotoxicity of survivin ASODN in the K562 cells. The morphologic changes in the nucleus and the apoptotic rate were observed by Hoechst33342/PI staining.Caspase-3 activity was evaluated by a kinase activity assay. The changes of survivin protein expression after transfection were detected by Western blots.RESULTS Eight hours after transfection, fluorescence in the K562 cells was well distributed. Treatment of the cells for 44 h with different concentrations of survivin ASODN produced a IC50 of 800 nmol/L. The growth inhibitory rate with 200, 400, 600 and 1000 nmol/L of survivin ASODN was 15.8±1.6%, 23.8±5.9%, 37.1±5.6% and 77.3±2.5% respectively. After 36 h of of survivin ASODN treatment, distinct morphologic changes characteristic of cell apoptosis such as karyopyknosis and conglomeration were observed by Hoechst33342/PI staining. Caspase-3 activity increased significantly after treatment of the cells with different concentrations of survivin ASODN (P<0.01)and following treatment with 800 nmol/L survivin ASODN, survivin expression decreased significantly.CONCLUSION Survivin ASODN exerts an anti-cancer effect by inducing apoptosis in K562 leukaemia cells. Up-regulated expression of caspase3 may play a role in this process.

  6. Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia.

    Directory of Open Access Journals (Sweden)

    Farhat L Khanim

    Full Text Available BACKGROUND: The majority of acute myeloid leukaemia (AML patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. PRINCIPAL FINDINGS: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ and the sex hormone medroxyprogesterone acetate (MPA against AML cell lines and primary AML cells. The combined activity of BEZ and MPA (B/M converged upon the increased synthesis and reduced metabolism of prostaglandin D(2 (PGD(2 resulting in elevated levels of the downstream highly bioactive, anti-neoplastic prostaglandin 15-deoxy Delta(12,14 PGJ(2 (15d-PGJ(2. BEZ increased PGD(2 synthesis via the generation of reactive oxygen species (ROS and activation of the lipid peroxidation pathway. MPA directed prostaglandin synthesis towards 15d-PGJ(2 by inhibiting the PGD(2 11beta -ketoreductase activity of the aldo-keto reductase AKR1C3, which metabolises PGD(2 to 9alpha11beta-PGF(2alpha. B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ(2. Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors. SIGNIFICANCE: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ(2. These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML.

  7. Metabolomic profiling of drug responses in acute myeloid leukaemia cell lines.

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    Stefano Tiziani

    Full Text Available Combined bezafibrate (BEZ and medroxyprogesterone acetate (MPA exert unexpected antileukaemic activities against acute myeloid leukaemia (AML and these activities are associated with the generation of reactive oxygen species (ROS within the tumor cells. Although the generation of ROS by these drugs is supported by preceding studies including our own, the interrelationship between the cellular effects of the drugs and ROS generation is not well understood. Here we report the use of NMR metabolomic profiling to further study the effect of BEZ and MPA on three AML cell lines and to shed light on the underlying mechanism of action. For this we focused on drug effects induced during the initial 24 hours of treatment prior to the onset of overt cellular responses and examined these in the context of basal differences in metabolic profiles between the cell lines. Despite their ultimately profound cellular effects, the early changes in metabolic profiles engendered by these drugs were less pronounced than the constitutive metabolic differences between cell types. Nonetheless, drug treatments engendered common metabolic changes, most markedly in the response to the combination of BEZ and MPA. These responses included changes to TCA cycle intermediates consistent with recently identified chemical actions of ROS. Notable amongst these was the conversion of alpha-ketoglutarate to succinate which was recapitulated by the treatment of cell extracts with exogenous hydrogen peroxide. These findings indicate that the actions of combined BEZ and MPA against AML cells are indeed mediated downstream of the generation of ROS rather than some hitherto unsuspected mechanism. Moreover, our findings demonstrate that metabolite profiles represent highly sensitive markers for genomic differences between cells and their responses to external stimuli. This opens new perspectives to use metabolic profiling as a tool to study the rational redeployment of drugs in new disease

  8. Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia.

    Science.gov (United States)

    Ridinger-Saison, M; Evanno, E; Gallais, I; Rimmelé, P; Selimoglu-Buet, D; Sapharikas, E; Moreau-Gachelin, F; Guillouf, C

    2013-09-01

    Deregulation of transcriptional networks contributes to haematopoietic malignancies. The transcription factor Spi-1/PU.1 is a master regulator of haematopoiesis and its alteration leads to leukaemia. Spi-1 overexpression inhibits differentiation and promotes resistance to apoptosis in erythroleukaemia. Here, we show that Spi-1 inhibits mitochondrial apoptosis in vitro and in vivo through the transcriptional repression of Bim, a proapoptotic factor. BIM interacts with MCL-1 that behaves as a major player in the survival of the preleukaemic cells. The repression of BIM expression reduces the amount of BIM-MCL-1 complexes, thus increasing the fraction of potentially active antiapoptotic MCL-1. We then demonstrate that Spi-1 represses Bim transcription by binding to the Bim promoter and by promoting the trimethylation of histone 3 on lysine 27 (H3K27me3, a repressive histone mark) on the Bim promoter. The PRC2 repressive complex of Polycomb is directly responsible for the deposit of H3K27me3 mark at the Bim promoter. SUZ12 and the histone methyltransferase EZH2, two PRC2 subunits bind to the Bim promoter at the same location than H3K27me3, distinct of the Spi-1 DNA binding site. As Spi-1 interacts with SUZ12 and EZH2, these results indicate that Spi-1 modulates the activity of PRC2 without directly recruiting the complex to the site of its activity on the chromatin. Our results identify a new mechanism whereby Spi-1 represses transcription and provide mechanistic insights on the antiapoptotic function of a transcription factor mediated by the epigenetic control of gene expression.

  9. Relationship between Hysteroscopic Findings and Leukaemia Inhibitory Factor in Mid-secretary Endometrium

    Institute of Scientific and Technical Information of China (English)

    Yu-bao WANG; Lu FANG; Zhong-mei LI; Xiao-yun WU; Zuan-chong FENG

    2003-01-01

    Objective To explore the potencial relationship between hysteroscopic findings,and the concentrationa of leukaemia inhibitory factor (LIF) in uterine flushing as well as the expression of LIF in the endometriumMethods Hysteroscopy was carried out among 64 infertile female patients and uterine flushing was collected for LIF assay in the mid-secretory phase. All subjects were classified according to the appearance of the glandular openings and the blood vessels on the endometrium surface into Group I and Group II. An ELISA kit specific for human LIF was used for LIF assay.Results The median LIF concentrations measured in Group I and Group II were 14.375±15.155 pg/mL and 61.696±44.127 pg/mL. The difference of LIF concentration was statistically significant (P<0.05) between Group I and Group II. But no significant difference between Group II and the proliferative endometrium (11.02±11.07 pg/mL) was found. The average expression of LIF mRNA in Group I was 0.93±0.20, and 1.55±0.08 in Group II. The expression of LIF mRNA in the endometrium from Group I was much lower than that from the decidua of early pregnancy (1.65±0.18), while no significant difference was observed between Group II and the decidua of early pregnancy.Conclusion There is a strong relationship between endoscopic findings and the concentration of LIF. Our data suggested that the hysteroscopic appearance of the mid-secretory endometrium and measurement of LIF in uterine flushing are better evaluation factors for the uterine receptivity.

  10. Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin

    Science.gov (United States)

    Khajavinia, Amir; Varshosaz, Jaleh; Jafarian Dehkordi, Abbas

    2012-10-01

    The aim of the present study was to evaluate the diverse properties of transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using three different fatty amines, including stearylamine (SA), dodecylamine (DA) and spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs were prepared by an emulsion-solvent evaporation method followed by probe sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage between the surface-exposed amino group of the fatty amine and the carboxyl group of the protein. The physical coating was performed in a Ringer-Hepes buffer medium. NLCs were characterized by their particle size, zeta potential, polydispersity index, drug entrapment percentage, drug release profiles and Tf-coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia cells was studied by MTT assay, and their cellular uptake was studied by a flow cytometry method. SA-containing NLCs showed the lowest particle size, the highest zeta potential and the largest coupling efficiency values. The drug entrapment percentage and the zeta potential decreased after Tf coupling, but the average particle size increased. SP-containing formulations released their drug contents comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors resulted in a significantly higher cell survival rate for Tf-NLCs. The highest cytotoxic activity was observed in the chemically coupled SA-containing nanoparticles, with an IC50 value of 15-fold lower than free etoposide.

  11. Feline leukaemia provirus load during the course of experimental infection and in naturally infected cats.

    Science.gov (United States)

    Hofmann-Lehmann, R; Huder, J B; Gruber, S; Boretti, F; Sigrist, B; Lutz, H

    2001-07-01

    Feline leukaemia virus (FeLV) infection in domestic cats can vary in its outcome (persistent, transient, no infection) for reasons that are not entirely known. It was hypothesized that the initial virus and provirus load could significantly influence the course of retrovirus infection. To determine the role of provirus loads, two methods of PCR, a nested PCR and a fluorogenic probe-based (TaqMan) real-time quantitative PCR, which were specific to the U3 region of FeLV-A were established. FeLV provirus in naturally and experimentally infected cats was then measured. Only 3 weeks after experimental FeLV-A infection, persistently infected cats demonstrated higher provirus loads and lower humoral immune responses than cats that had overcome antigenaemia. Lower initial provirus loads were associated with successful humoral immune responses. Unexpectedly, provirus in the buffy-coat cells of two cats that tested negative for the p27 antigen (a marker for viraemia) was also detected. In 597 Swiss cats, comparison of p27 antigen levels with PCR results revealed broad agreement. However, similar to the experimental situation, a significant number of animals (10%) was negative for the p27 antigen and FeLV-positive by PCR. These cats had a mean provirus load 300-fold lower than that of animals testing positive for the p27 antigen. In conclusion, an association between the provirus load and the outcome of FeLV infection was found. Detection of provirus carriers should contribute to further the control of FeLV. In addition, quantification of provirus loads will lead to a better understanding of FeLV pathogenesis and anti-retrovirus protective mechanisms.

  12. Childhood depression: a systematic review

    Directory of Open Access Journals (Sweden)

    Lima NNR

    2013-09-01

    Full Text Available Nádia Nara Rolim Lima,1 Vânia Barbosa do Nascimento,1 Sionara Melo Figueiredo de Carvalho,1 Luiz Carlos de Abreu,1,3 Modesto Leite Rolim Neto,2 Aline Quental Brasil,2 Francisco Telésforo Celestino Junior,2 Gislene Farias de Oliveira,2 Alberto Olavo Advíncula Reis3 1Programa de Pós-graduação em Ciências da Saúde, Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil; 2Departamento de Medicina. Universidade Federal do Ceará, UFC, Barbalha, Ceará, Brazil; 3Departamento de Saúde Materno Infantil, Faculdade de Saúde Pública, Universidade de São Paulo, São Paulo, Brazil Abstract: As an important public health issue, childhood depression deserves special attention, considering the serious and lasting consequences of the disease to child development. Taking this into consideration, the present study was based on the following question: what practical contributions to clinicians and researchers does the current literature on childhood depression have to offer? The objective of the present study was to conduct a systematic review of articles regarding childhood depression. To accomplish this purpose, a systematic review of articles on childhood depression, published from January 1, 2010 to November 24, 2012, on MEDLINE and SciELO databases was carried out. Search terms were “depression” (medical subject headings [MeSH], “child” (MeSH, and "childhood depression" (keyword. Of the 180 retrieved studies, 25 met the eligibility criteria. Retrieved studies covered a wide range of aspects regarding childhood depression, such as diagnosis, treatment, prevention and prognosis. Recent scientific literature regarding childhood depression converge to, directly or indirectly, highlight the negative impacts of depressive disorders to the children's quality of life. Unfortunately, the retrieved studies show that childhood depression commonly grows in a background of vulnerability and poverty, where individual and familiar needs

  13. Childhood Sexual Abuse

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    Evrim Aktepe

    2009-08-01

    Full Text Available Sexual abuse is defined as use of child or adolescent by the adults for satisfying of sexual urges and needs with forcing, threatening or tricking. Sexual abuse can be in the form of sexual abuse without touch, sexual touch, interfemoral intercourse, sexual penetration, and sexual exploitation. The prevalence of sexual abuse is reported as 10-40%. It is seen in female four times more than in males. Abusers are frequently male, only 5-15% of them are female. The abuse by females is usually towards male child. Thirty-fifty percent of abuse cases among child and adolescent are outside the family including strangers or familiar person. Some features of abusers are introvert personality, pedophilic and antisocial personality. Most of the abusers have a history of sexual abuse or aggression during childhood. Sexual intercourse between two people who are not allowed to marry by law is called as incest. Family pattern of incest is defined globally as disorganized and dysfunctional. The most commonly reported familial pattern is rigid and patriarchal family pattern with a harsh father using force quite frequently. The clinical features and impacts of the sexual abuse on the child varies according to the relation between abusers and the child, form of abuse, duration of abuse, presence of physical assault, developmental phase, child age and psychological development before the abuse. Sexual abuse history may result in psychiatric disorders including anxiety, depression, substance dependence, suicide act, borderline personality disorder, posttraumatic stress disorder. Abuse negatively affects interpersonal relationships and self esteem of abused individuals. Several studies reported close association between risky sexual behaviors in adulthood and a history of of sexual abuse during childhood. Four traumatic dynamics including traumatic sexuality with abuse, feeling of betrayal, weakness, and stigmatization exist in childhood abuse. Trauma can cause

  14. Peer Bullying During Early Childhood

    Directory of Open Access Journals (Sweden)

    Hatice UYSAL

    2012-10-01

    Full Text Available Peer bullying during early childhood is discussed along with the literature reviewed in this article with the purpose of drawing attention to peer bullying during early childhood and its significance, and contributing to studies which are few in number in Turkey. Peer bullying during early childhood was considered with its definition and types, people who play key roles in peer bullying, factors (gender, age, parents, and friendship that relate to peer bullying, and what should be done before and after peer bullying.

  15. Effects of pharmacological and genetic disruption of CXCR4 chemokine receptor function in B-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Randhawa, Shubhchintan; Cho, Byung S; Ghosh, Dipanjan; Sivina, Mariela; Koehrer, Stefan; Müschen, Markus; Peled, Amnon; Davis, Richard E; Konopleva, Marina; Burger, Jan A

    2016-08-01

    B cell acute lymphoblastic leukaemia (B-ALL) cells express high levels of CXCR4 chemokine receptors for homing and retention within the marrow microenvironment. Bone marrow stromal cells (BMSC) secrete CXCL12, the ligand for CXCR4, and protect B-ALL cells from cytotoxic drugs. Therefore, the therapeutic use of CXCR4 antagonists has been proposed to disrupt cross talk between B-ALL cells and the protective stroma. Because CXCR4 antagonists can have activating agonistic function, we compared the genetic and pharmacological deletion of CXCR4 in B-ALL cells, using CRISPR-Cas9 gene editing and CXCR4 antagonists that are in clinical use (plerixafor, BKT140). Both genetic and pharmacological CXCR4 inhibition significantly reduced B-ALL cell migration to CXCL12 gradients and beneath BMSC, and restored drug sensitivity to dexamethasone, vincristine and cyclophosphamide. NOD/SCID/IL-2rγnull mice injected with CXCR4 gene-deleted B-ALL cells had significant delay in disease progression and superior survival when compared to control mice injected with CXCR4 wild-type B-ALL cells. These findings indicate that anti-leukaemia activity of CXCR4 antagonists is primarily due to CXCR4 inhibition, rather than agonistic activity, and corroborate that CXCR4 is an important target to overcome stroma-mediated drug resistance in B-ALL. PMID:27071778

  16. CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis.

    Science.gov (United States)

    Yoshida, Noriaki; Miyoshi, Hiroaki; Kato, Takeharu; Sakata-Yanagimoto, Mamiko; Niino, Daisuke; Taniguchi, Hiroaki; Moriuchi, Yukiyoshi; Miyahara, Masaharu; Kurita, Daisuke; Sasaki, Yuya; Shimono, Joji; Kawamoto, Keisuke; Utsunomiya, Atae; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi

    2016-04-01

    Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology.

  17. Violacein induces death of resistant leukaemia cells via kinome reprogramming, endoplasmic reticulum stress and Golgi apparatus collapse.

    Directory of Open Access Journals (Sweden)

    Karla C S Queiroz

    Full Text Available It is now generally recognised that different modes of programmed cell death (PCD are intimately linked to the cancerous process. However, the mechanism of PCD involved in cancer chemoprevention is much less clear and may be different between types of chemopreventive agents and tumour cell types involved. Therefore, from a pharmacological view, it is crucial during the earlier steps of drug development to define the cellular specificity of the candidate as well as its capacity to bypass dysfunctional tumoral signalling pathways providing insensitivity to death stimuli. Studying the cytotoxic effects of violacein, an antibiotic dihydro-indolone synthesised by an Amazon river Chromobacterium, we observed that death induced in CD34(+/c-Kit(+/P-glycoprotein(+/MRP1(+ TF1 leukaemia progenitor cells is not mediated by apoptosis and/or autophagy, since biomarkers of both types of cell death were not significantly affected by this compound. To clarify the working mechanism of violacein, we performed kinome profiling using peptide arrays to yield comprehensive descriptions of cellular kinase activities. Pro-death activity of violacein is actually carried out by inhibition of calpain and DAPK1 and activation of PKA, AKT and PDK, followed by structural changes caused by endoplasmic reticulum stress and Golgi apparatus collapse, leading to cellular demise. Our results demonstrate that violacein induces kinome reprogramming, overcoming death signaling dysfunctions of intrinsically resistant human leukaemia cells.

  18. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Science.gov (United States)

    Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy. PMID:25821830

  19. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Directory of Open Access Journals (Sweden)

    Elva Jiménez-Hernández

    2015-01-01

    Full Text Available Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients, diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients, diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P=0.041. Overall survival for Group A (18, 90% was higher than that for Group B (60%. Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

  20. Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.

    Science.gov (United States)

    Sive, J I; Basilico, S; Hannah, R; Kinston, S J; Calero-Nieto, F J; Göttgens, B

    2016-01-01

    Transcriptional dysregulation is associated with haematological malignancy. Although mutations of the key haematopoietic transcription factor PU.1 are rare in human acute myeloid leukaemia (AML), they are common in murine models of radiation-induced AML, and PU.1 downregulation and/or dysfunction has been described in human AML patients carrying the fusion oncogenes RUNX1-ETO and PML-RARA. To study the transcriptional programmes associated with compromised PU.1 activity, we adapted a Pu.1-mutated murine AML cell line with an inducible wild-type PU.1. PU.1 induction caused transition from leukaemia phenotype to monocytic differentiation. Global binding maps for PU.1, CEBPA and the histone mark H3K27Ac with and without PU.1 induction showed that mutant PU.1 retains DNA-binding ability, but the induction of wild-type protein dramatically increases both the number and the height of PU.1-binding peaks. Correlating chromatin immunoprecipitation (ChIP) Seq with gene expression data, we found that PU.1 recruitment coupled with increased histone acetylation induces gene expression and activates a monocyte/macrophage transcriptional programme. PU.1 induction also caused the reorganisation of a subgroup of CEBPA binding peaks. Finally, we show that the PU.1 target gene set defined in our model allows the stratification of primary human AML samples, shedding light on both known and novel AML subtypes that may be driven by PU.1 dysfunction.