Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A search of the records of 10 pediatric oncology centers revealed 102 children with more than one malignant neoplasm. In this group of 102 patients, all pediatric cancers were seen as initial lesions, but Wilms' tumor and retinoblastoma were over-represented and leukemia and brain tumors underrepresented. Survival variation as well as tumor susceptibility may be responsible for this disproportion. Osteosarcomas and chondrosarcomas were the most frequent second malignant neoplasms (SMN). Embryonal tumors were rare as SMN and adult-type tumors (carcinomas) appeared at earlier than expected ages, whether arising after irradiation or not related to that form of therapy. Radiation was associated with 69 SMN, genetic disease accounted for 27 SMN and both conditions were noted in 15 SMN. In the group of 21 patients for whom neither radiation nor a known genetic disorder could be implicated, there were three with colon carcinoma and glioma and five with leukemia or lymphoma and glioma. These combinations may reflect new tissue-specific hereditary cancer syndromes.
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PMID:Patterns of second malignant neoplasms in children. 19 10

Ataxia-telangiectasia is a rare genetic disorder associated with immune deficiency, chromosome instability, and a predisposition to lymphoid malignancy. We have detected chromosomally anomalous clones of lymphocytes in eight patients with this disorder. Chromosome banding disclosed that the clones are consistently marked by structural rearrangement of the long arm (q) of chromosome 14. A translocation involving 14q was found in clones obtained from seven of the eight patients whereas a ring 14 chromosome was found in a clone obtained from the other. These findings as well as data obtained by others for patients with ataxia-telangiectasia suggest that structural rearrangement of 14q is the initial chromosomal change in lymphocyte clones of patients with this disorder. Chromosomes of lymphocytes from one of the patients were studied before and after the onset of chronic lymphocytic leukemia. Before leukemia was diagnosed, the patient had a lymphocyte clone with a 14q translocation. This clone appears to have given rise to the leukemic cells. We hypothesize that structural rearrangement of 14q is directly related to abnormal growth of lymphocytes and that it may be a step toward the development of lymphoid malignancies. Increasing evidence, provided by others, for the nonrandom involvement of 14q in African-type Burkitt's lymphoma and other lymphoid neoplasms further strengthens this hypothesis.
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PMID:Somatic rearrangement of chromosome 14 in human lymphocytes. 105 13

The past 20 years of curative therapeutics of childhood acute leukaemia has been largely a period of consolidation of gains, refinement of techniques and dissemination of expertise and technology. However, certain lessons have been learned. First, cure can be permanent but the complexity and cost of curative treatment currently restricts its accessibility; prevention or simple curative treatment is needed. Secondly, cure of the child demands that the risk of adverse sequelae of treatments be carefully balanced with known therapeutic benefits. Thirdly, preventive meningeal irradiation is no longer required. Fourth, treatment intensification is self-limiting. Adverse reactions can cancel out or exceed therapeutic benefits, resulting in a lower cure rate or a similar cure rate with lower quality of cure. Finally, morphology, immunophenotype and genotype of acute leukaemia are important criteria for selecting and scheduling drug therapy. Genotype may be the most important since leukaemia is a genetic disorder for which morphology and immunophenotype are mere reflections. However, none of these features, individually or together, are sufficient to explain all the difference in outcome among children on a given treatment plan or to completely fulfill the need of criteria for selection of treatment. Acute leukaemia remains an unsolved problem demanding considerably more basic and clinical research to meet the need for prevention and simple dependable curative treatment.
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PMID:Lessons from 20 years of curative therapy of childhood acute leukaemia. 173 9

We have reviewed the records of the 16,564 cases of childhood cancer diagnosed from 1971 to 1983 which were reported to the National Registry of Childhood Tumours in Great Britain for the presence of underlying genetic disease in order to estimate the proportion which results from inherited mutations. A genetic condition was listed for 509 patients, or 3.07% of the total number of tumours. The most frequently recorded diagnoses were: bilateral retinoblastoma (162 cases); Down syndrome (135); neurofibromatosis (90); hereditary Wilms' tumour (71); and tuberous sclerosis (20). The highest hereditary fractions at individual tumour sites were seen for: retinoblastoma (37.2%); kidney (7.2%); leukaemia (2.6%) and brain and spinal cord (2.0%). When information about family history from published reports was incorporated into the figures calculated from Registry data the total genetic fraction was estimated to be 4.2%. We conclude that there is a clear genetic basis for a small minority of the cancers of childhood, but ethnic variation and the lack of known environmental determinants suggest that the total influence of heredity may be higher.
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PMID:An estimate of the heritable fraction of childhood cancer. 206 56

The expression of three EBV open reading frames (ORF's), BBRF3, BILF1 and BMRF2 in Epstein-Barr virus (EBV)-transformed B lymphocytes from ataxia-telangiectasia (A-T) homozygotes, was studied. A-T is a human recessive genetic disorder which predisposes homozygotes and heterozygotes to cancer. Computer analysis (Robson-Garnier) was used to study the secondary structure of EBV ORF's. Three ORF's (BBRF3, BILF1 and BMRF2) found by the Kyte and Doolittle computer method to have multiple hydrophobic domains in the putative polypeptides were selected, and the polypeptides were selected, and the respective cloned EBV DNA fragments were used as probes to detect mRNA in the normal and L-6 A-T lines that was not present in the L-15 A-T line. The probe for BILF1 detected two mRNA species (3.7 and 2.0 kb) in the normal lymphoblastoid and A-T L-6 lines, while only the 3.7 kb mRNA was expressed in the A-T L-15 lymphoblasts. The probe for BMRF2 detected two mRNA species (3.7 and 2.1 kb) in the EBV-transformed normal lymphoblasts and in one A-T line (L6). The BMRF2 mRNAs were not detected in the other A-T line (L-15). This study indicated that regulation of the three EBV genes in two EBV-transformed A-T lymphoblastoid lines, differs from that in the EBV-transformed normal lymphoblastoid line. In the A-T line L-6, the three EBV genes were expressed as in EBV-transformed lymphoblastoid cells originating from a normal donor (L-21) and in the P3HR1 Burkitt's lymphoma cell line. The A-T line L-15 differed from L-6 and the other cell lines in that it expressed only one (3.7 kb) RNA species from BILF1 ORF, while ORFs BBRF3 and BMRF2 were not expressed. Since A-T L-15 line contains EBV DNA genomes, and EBV VCA is not present in these cells prior to or after TPA treatment, it is suggested that EBV gene expression is regulated by these A-T lymphoblastoid cells in a manner different from that which operates in other EBV transformed cell lines.
Leukemia 1988 Dec
PMID:Differential expression of Epstein-Barr virus (EBV) genes BBRF3, BILF1, and BMRF2 in EBV-transformed lymphoblastoid lines from ataxia-telangiectasia patients. 284 95

Fanconi's anemia is a rare genetic disorder associated with congenital deformities, infections, chromosomal abnormalities, and leukemia. This brief article describes the case of a 20 year old man affected with the disease, who was given 100 mg daily of oxymetholone to cure leukopenia and thrombocytopenia. 10 months later he died of hepatic failure. Autopsy revealed hepatoma and liver peliosis, a rare condition of unknown etiology characterized by blood-filled cysts in the liver. It is possible that in the case reported here the hepatoma could have been related to the oxymetholone treatment, which conceivably could have initiated hepatic damage.
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PMID:Hepatoma and peliosis hepatis developing in a patient with Fanconi's anemia. 432 28

Marrow transplantation is effective treatment for a number of haematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is generally successful when used early in the treatment of aplastic anaemia. It is the only treatment that offers long-term disease-free survival for patients with acute leukaemia who have relapsed at least once, with 10-30 per cent apparent cures. Although still somewhat controversial, it appears also to be the treatment of choice for patients with acute non-lymphoblastic leukaemia in first chemotherapy induced remission and for those with chronic myelogenous leukaemia in the chronic phase since approximately 50-60 per cent of these patients are surviving after marrow transplantation in complete remission, apparently cured. Marrow grafting is the only effective treatment for many patients with inherited immunological-deficiency diseases and certain genetic storage diseases. It is being explored for the therapy of patients with lymphoma, Hodgkin's disease, multiple myeloma, small-cell lung cancer, testicular cancer, ovarian cancer and genetic disorders of haematopoiesis. Cures of congenital Fanconi anaemia, Blackfan-Diamond anaemia, osteopetrosis, and paroxysmal nocturnal haemoglobinuria have been achieved by marrow grafting. Genetic disorders associated with haemolytic anaemia and cyclic neutropenia have been cured by marrow grafting in animals. Target disorders for marrow transplantation in humans are thalassaemia major and sickle cell disease, and, indeed, a first successful transplant for treatment of thalassaemia major has recently been described (Thomas et al, 1982). Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. The Seattle team has now explored the use of less well-matched family member donors in more than 80 patients with leukaemia. These donors share one HLA haplotype genetically with the patient and are phenotypically identical at two of the three major HLA loci on the other HLA haplotype (Clift et al, 1979). Overall, the post-transplant survival appears more a reflection of the type and stage of the leukaemia than of the marrow donor. Patients with leukaemia grafted in relapse have a projected survival of 20-30 per cent and those transplanted in remission of 50 per cent. The incidence and severity of GVHD may not be significantly different from that of patients given HLA-identical sibling marrow grafts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Application of bone marrow transplantation in leukaemia and aplastic anaemia. 635 79

The question of radiological mass screening for congenital dislocated hip is still debated. We have tried to evaluate the cost-benefit ratio of radiological detection at the age of 3-4 months, taking into account the socio-economic cost and radiation risk. Assuming a frequency of this disorder of 1% the average cost of treatment of one case detected by X-ray screening at the age of 3-4 months, including the price of X-ray examinations of 99 normal babies, is 23,374 FF. The average cost of treatment of a case detected when walking (i.e. after 9 months) is 84,230 FF. The cost-benefit ratio is 3.6. In countries where the frequency reaches 2% the cost benefit ratio is 4.57. It also appears from our study that the irradiation of the patient is much smaller when the diagnosis is made earlier. Comparing the slight irradiation delivered to normal infants by this mass screening to the heavy irradiation received by a few individuals whose treatment is started after 9 months, the calculated risk of leukemia or of genetic disorder for the whole population still favours a systematic X-ray film of the pelvis at age 3-4 months. However, if it were decided to make obligatory this mass radiological detection programme during the fourth month of life, this would necessitate a serious effort to train all radiologists to obtain adequate films with the best radiation protection.
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PMID:Cost-benefit evaluation of systematic radiological diagnosis of congenital dislocated hip. 643

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.
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PMID:Bone marrow transplantation for Fanconi anemia. 767 Jan 20

Sickle cell anaemia is a hereditary disorder commonly seen in the black population, due to a point mutation in the beta globin gene. The sickle mutation is responsible for an increased rigidity and adherence of the red blood cell leading to haemolytic anaemia and vaso-occlusive episodes. Symptoms include dactylitis, painful crisis, splenic sequestration and the development of multi-organ damage and failure. The progressive loss of splenic function increases the risk of infections. The morbidity and mortality can be reduced by the maintenance of an adequate nutrition, the prevention of infection and the treatment of complications. In some patients severely affected, a chronic transfusion program has to be instigated to maintain a level of haemoglobin S below 50%. New therapeutic strategies include the use of hydroxyurea and maybe, in the future, butyrates to increase the level of foetal haemoglobin. Further studies are needed to evaluate the benefits of such therapies. Bone marrow transplantation represents an attractive therapeutic tool and its role in other haemoglobinopathies like thalassaemia is now well demonstrated. As far as sickle anaemia is concerned, the first report concerned a child with acute myeloblastic leukaemia. The patient is now cured of both the sickle cell anaemia and the leukemia. Since April 1986, 21 patients underwent an allogeneic bone marrow transplantation for sickle cell anaemia in our department. 20 patients became asymptomatic and have an electrophoretic pattern of the haemoglobin similar to that of the donor. One patient died of bone marrow transplantation related complications.
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PMID:Bone marrow transplantation in sickle cell anaemia. 846 26


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