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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two boys with Down's syndrome, recognized at birth, developed acute myelogibrosis at the ages of 19 and 21 months. The disorder presented with anaemia and splenomegaly, and clinically resembled acute leukaemia, but bone marrow histology showed a bizarre pattern with generalized fibrosis, markedly increased reticulin, large reticulum cells, and giant cells resembling megakaryocytes. The children survived 6 and 11 months from diagnosis. A third case is quoted (Hillman and Forrester, 1968) which was also studied at this hospital; the features of all 3 cases are similar. There appears to be an increased incidence of acute myelofibrosis in children with Down's syndrome, which may be a further example of the instability of the haemopoietic system in the disease. In children with Down's syndrome and unusual leukaemia-like illness, histological examination of the bone marrow may be diagnostic.
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PMID:Acute myelofibrosis in children with Down's syndrome. 12 73

DNA-repair and the frequency of chromosome aberration after u.v. and X-ray irradiation was studied on leukocytes from patients with Down's syndrome. The u.v.-induced DNA-repair synthesis was followed by the incorporation of [3H]thymidine in the presence of hydroxyurea. Similar dose-response curves were established for Down's syndrome leukocytes and controls. The cells from patients with Down's syndrome incorporated 70-75% of the activity of control cells at the various doses (32-196 erg/mm.2). This difference was significant for the two highest u.v.-doses (P less than 0-01). The yield of dicentric chromosomes after X-ray exposure (150 rad.) was 35% higher in Down's syndrome leukocytes than in the control cells (P less than 0-001). Combined u.v. and X-ray irradiation caused a twofold increase in the frequency of dicentric chromosomes in control cells, while the increase was only 27% in Down's syndrome leukocytes. This synergistic effect of u.v. and X-ray irradiation on the yield of dicentric chromosomes suggests that healing of X-ray and u.v.-induced DNA lesions may partly utilize the same repair enzymes. The results also indicate that DNA repair mechanisms are impaired in leukocytes from patients with Down's syndrome, which may contribute to the increased incidence of leukemia and the susceptibility to X-ray irradiation in this disorder.
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PMID:DNA repair and frequency of x-ray and u.v.-light induced chromosome aberrations in leukocytes from patients with Down's syndrome. 13 31

The frequency of chromosomal aberrations produced by X-rays is greater in lymphocytes cultured from trisomy 21 patients (Down's syndrome) than from normal diploid donors. This increase, which can be detected by a micronucleus assay for chromosomal damage, was postulated by us to result from a defect in the rejoining system which repairs chromosomal breaks. The postulated defect would result in a longer rejoining time, therapy permitting more movement of broken ends and thus enhancing the frequency of exchanges. To test this possibility, the time required for the rejoining (repair) of chromosome breaks was measured in lymphocytes from five Down's syndrome (four trisomy 21 and one D/G translocation partial trisomy 21) donors, from a monosomy 21 donor, and from five diploid donors. The rejoining time was reduced in the Down's syndrome lymphocytes in comparison to the normal diploid and monosomy 21 lymphocytes. Thus the repair of chromosome breaks, far from being defective as evidenced by a longer rejoining time in Down's syndrome cells, occurred more rapidly than in normal cells. A mechanism is proposed by which reduced rejoining times would increase aberration frequencies as a consequence of competition between a (hypothetical) error-free repair system and the error-prone repair system that generates chromosomal aberrations. We suggest that the alteration in the rejoining of chromosomal aberrations may underlie the increased susceptibility of people with Down's syndrome to leukemia.
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PMID:The repair of X-ray induced chromosomal damage in trisomy 2-and normal diploid lymphocytes. 13 77

The effect of leukaemia-associated antigens prepared from leukaemic lymphoblasts and myeloblasts has been studied on the migration of peripheral leucocytes obtained from children with Down's syndrome. Membrane extract from leukaemic lymphoblasts had no effect, while that from leukaemic myeloblasts was slightly inhibitory, i.e. it was "recognized" as antigen by the lymphocytes of children with Downs syndrome.
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PMID:Leucocyte migration in presence of leukaemia-associated antigens in children with Down's syndrome. 13 41

Electron microscopical and haematological investigation of peripheral blood has shown a higher percentage of leukaemia-like nuclear ultrastructural abnormalities in the leucocytes of 30 individuals with Down's syndrome (mean 6.3%) than in normal controls (mean less than 1%). Most of these aberrations consisted of nuclear membrane abnormalities. Red cell folate values were very low in the group with Down's syndrome. Although mean serum folate and vitamin B12 levels were normal in this group, these individuals displayed increasing macrocytosis and decreasing serum folate levels with age. The whole group with Down's syndrome showed an increased mean corpuscular volume (MCV). The percentage of ultrastructural abnormalities did not correlate with folate levels when they were analysed individually. The existence of nuclear membrane abnormalities and folate deficiency, both of which may be associated with increased chromosome breakage, may be partly responsible for the increased leukaemia risk in patients with Down's syndrome.
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PMID:Leucocyte ultrastructure and folate metabolism in Down's syndrome. 13 96

530 children with acute lymphoblastic leukaemia were diagnosed between 1. 1. 1971 and 31. 12. 1974, and treated at 35 German hospitals according to the Memphis study VII or VIII2 and subsequently followed until 31. 12. 1976. At diagnosis 17.2% of the patients had a WBC count of over 50,000/mm3, 8.9% had mediastinal enlargement, 2.1% CNS leukaemia and 1.7% Down's syndrome. After being treated for two and a half years and being observed for a maximum of six years (minimum two years) 262 children (49.4%) were living, 203 (38.8%) in continued complete remission, most of them one to three years after end of treatment. Primary bone marrow relapse occurred in 39.6%, but CNS relapse in only 8.7%. Cranial irradiation at a dose of 1800 rad in 70 patients produced a CNS relapse of only 7.1%. Forty-one of these 530 children (7.7%) died in continued complete remission, the main causes being interstitial pneumonia and varicella. There was no difference in initial features and treatment results between six centres which had many and 29 with rather fewer patients. The five-years-survival rate (life-table method) was 41 +/- 3.5% for all 530 children and 10 +/- 3.7% for the 92 children with initial leucocyte counts of over 50.000/mm3.
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PMID:[Combination chemotherapy and cranial irradiation in 530 children with acute lymphoblastic leukaemia (author's transl)]. 14 70

Relatives of probands with histologically confirmed Alzheimer's disease had excessive morbidity from Alzheimer's disease, Down's syndrome, and hematologic malignancies. These associations coupled with two previously reported ones, the indistinguishable histopathological changes in brain in Alzheimer's disease and Down's syndrome, and the 20-fold increased incidence of leukemia among persons with Down's syndrome, are evidence that some instances of those disorders are associated with a unitary genetic etiology. The genetic defect may be expressed through disorganization of microtubules. Other evidence suggests that the same process may be involved in aging and in other chromosomal aberrations.
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PMID:The genetics of Alzheimer's disease: associations with hematologic malignancy and Down's syndrome. 14 59

There is an increased incidence of acute leukemia in patients with Down's syndrome patients have a trisomy-21 chromosomal pattern, and chromosomal abnormalities can be seen in acute leukemia. It is possible that the increased incidence of acute leukemia in Down's syndrome persons may be due in part to their chromosomal abnormalities. Such abnormalities, some appearing in a stepwise clonal evolution, were found in five Down's syndrome patients, four with acute leukemia and one with abnormal regulation of leukopoiesis. Morphological abnormal chromosomes were also found in three patients. These chromosomal abnormalities are similar to those seen in non-Down's syndrome leukemic patients. There is suggestive evidence for clonal evolution hypothesis of luekemogenesis in non-Down's syndrome patients. The abnormal chromosomal pattern reported in our Down's syndrome patients could be the result of nondisjunction in mitosis, and leukemia may be the phenotypical expression of this nondisjunction.
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PMID:Down's syndrome and leukemia: mechanism of additional chromosomal abnormalities. 14 44

Congenital leukaemia is a rare disease with approximately 100 cases reported in the literature. It is most often diagnosed as acute myelogenous leukaemia (AML). Leukaemic skin nodules and hepatosplenomegaly are the most frequent clinical findings noted. The laboratory manifestations include a markedly elevated white count with a large percentage of blasts, and a bone marrow aspirate that is cellular with a monotonous population of immature cells. Neonatal leukaemoid and leucoerythroblastic reactions may cause diagnostic confusion. In particular, the neonate with Down's syndrome can manifest either AML or a profound transient myeloproliferative syndrome that is clinically and haematologically indistinguishable from congenital AML. In contrast to congenital leukaemia, however, this myeloproliferative syndrome is transient and resolves spontaneously without anti-leukaemia therapy. On the other hand, untreated congenital leukaemia is a fatal disease. For this reason it is important to establish early diagnosis of congenital leukaemia and institute therapy. Treatment programmes should be modelled after established childhood programmes for acute lymphocytic leukaemia and acute myelogenous leukaemia.
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PMID:Congenital leukaemia and the neonatal myeloproliferative disorders associated with Down's syndrome. 14 90

The number of granulocytic progenitor cells (colony forming units in culture: CFUc) in the blood of patients with Down's syndrome was found to be reduced by 73.2% when compared to a group of age and sex matched controls. However, the blood CFUc of the Down's syndrome patients and the controls showed similar sensitivity to hydroxyurea which suggests that the low number of progenitor cells in Down's syndrome is not compensated by a marked increase in their cellular proliferation. The colony size distributions were similar for both the patients and the controls and, in addition, repeated assays at various intervals revealed no marked fluctuation in the number of blood CFUc in either group. The significance of the reduced number of circulating CFUc in Down's syndrome in relation to the known susceptibility of such patients to leukaemia is discussed.
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PMID:Reduced number of peripheral blood granulocytic progenitor cells in patients with Down's syndrome. 15 71


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