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)

Patients with Fanconi's anemia (FA) are at a high risk for development of malignancies. It is well-known that leukemia occurs in approximately 10% of cases, with increasing risk with age. Less commonly recognized is the risk for myelodysplastic syndromes (approximately 5%); the relationship between myelodysplasia and evolution to leukemia remains speculative. What also needs to be emphasized is that older patients have an ever-increasing risk for development of solid tumors, with at least 5% reported to have liver tumors (male:female ratio, 2:1) and an equal number of other cancers (female:male ratio, 3:1, even after exclusion of gynecologic malignancies). Hematologists have tended to focus on aplastic anemia and leukemia. As FA patients live longer, more of the other malignancies will occur, perhaps related to cord blood or bone marrow transplant, or treatment with cytokines. This review identifies the types of tumors for which patients with Fanconi's anemia are at risk.
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PMID:Fanconi's anemia and malignancies. 889 34

Most of the primates, unlike other mammals, have mutations in urate oxidase gene and cannot catabolize urate in the bodies. In addition to the genetic defects, some human subjects have various abnormalities in urate metabolism. Urate metabolism abnormalities are classified into two categories, hyperuricemia and hypouricemia. Usually, the urate pool size of an adult male is about 1,200 mg, and 700 mg urate is produced daily. The production is balanced by the excretion of urate into urine (500 mg) and intestine (200 mg). If this balance is disturbed, either hyperuricemia or hypouricemia occurs. According to the mechanisms, hyperuricemia is classified into overproduction and underexcretion, and hypouricemia into underproduction and overexcretion. Overproduction of ruate is caused by PRPP synthetase superactivity, HPRT deficiency, leukemia and alcohol ingestion. Underexcretion of urate is caused by renal insufficiency and treatment by diuretics. Underproduction of urate is caused by xanthine dehydrogenase deficiency, purine nucleoside deficiency and allopurinol treatment. Overexcretion of urine is caused by familial renal hypouricemia, Fanconi's syndrome, diabetes mellitus and treatments with benzbromarone and probenecid. All of these conditions are classified, according to other aspects, into primary and secondary, and genetic and non-genetic abnormalities.
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PMID:[Abnormalities in urate metabolism: concept and classification]. 897 99

Clinical evidence for a link between aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH) and hypoplastic leukaemia is provided by studies of clonal disorders, which may be a complication of congenital or acquired aplastic anaemia. Fanconi's anaemia is the most common congenital disorder and leukaemia occurs in at least 10% of cases. In acquired aplastic anaemia, a high incidence of myelodysplastic syndrome (MDS) was noted in patients with aplastic anaemia, seemingly cured of their aplasia by antilymphocyte globulins (ALG). In a recent survey, the 10-year cumulative incidence rates were 9.6% for MDS, 6.6% for acute leukaemia (115-fold higher than in the general population). Biological evidence is provided by bone marrow morphology, as a certain degree of dysmyelopoiesis is not unusual in aplastic anaemia. Cytogenetic analyses in aplastic anaemia are scarce, but data have shown clonal cytogenetic abnormalities at diagnosis in otherwise typical aplastic anaemia. Recently, flow cytometry to assess the glycosyl-phosphatidylinositol (GPI) molecule defect in PNH has demonstrated that a significant proportion of patients with otherwise typical aplastic anaemia have, in fact, a GPI defect due to alterations within the PIG-A gene. Finally, aplastic anaemia patients were recently reported to have molecular evidence of clonal haematopoiesis; this must now be discussed in light of recent clonality studies in normal individuals. The clinical and biological evidence for a link between aplastic anaemia, PNH and hypoplastic leukaemia allows the generation of a model of aplastic anaemia as a possible pre-pre-leukaemic disorder.
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PMID:Could aplastic anaemia be considered a pre-pre-leukaemic disorder? 898 43

We examined five children who underwent allogeneic peripheral stem cell transplantation (PSCT) using positively selected CD34+ cells from three or two loci-mismatched donors. CD34+ cells mobilized from peripheral blood were separated by immunomagnetic beads. CD34+ cells at 2.2-6.2 x 10(6)/kg were transplanted into three patients with refractory leukemia, a patient with relapsed medulloblastoma and a patient with Fanconi's anemia following a conditioning regimen which included irradiation, alkylating agents and antithymocyte globulin treatment. The number of infused CD3+ cells included in grafts was 2.3-22.7 x 10(4)/kg. Four patients achieved engraftment and hematopoietic reconstitution (> 5 x 10(8)/l of neutrophils on day 10 or 11). Graft rejection was observed in the patient with Fanconi's anemia, but a rapid engraftment was obtained after second PSCT. Although no prophylactic agents other than ATG (included in the conditioning regimen) were used, greater than grade I acute GVHD was not observed, but limited chronic GVHD was observed in two patients. The two patients with leukemia relapsed on days 103 and 210, respectively, and the patient with medulloblastoma died of disease on day 159. The patient with Fanconi's anemia died of fungal infection. CMV and HHV-6 diseases developed in four and two patients, respectively. Thus, although SCT using positively selected peripheral CD34+ cells may be an alternative approach for overcoming graft rejection and GVHD from HLA- mismatched donors, persistent immune deficiency attributing to extremely low numbers of T cells in grafts can potentially lead to reactivation of herpes viruses.
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PMID:Allogeneic peripheral stem cell transplantation using positively selected CD34+ cells from HLA-mismatched donors. 950 68

After studying of familial leukemias, Myelodysplastic Syndrome (MDS) and aplastic anemia (AA), we observed and analysed bone marrow (BM) cells hematologically and molecular-cytogenetically in 36 persons who are first degree relatives (FDRs) of patients with acute leukemias (AL), MDS and AA. The peripheral blood (PB) lymphocyte chromosome fragility sensitive to folic acid and unstability was also analysed in 18 FDRs. The abnormal BM megakaryocystic/erythroid cellularity and the rearrangement of c-erbB were found in 66%-86.1% of parents and siblings of patients. The associations of dysplastic megakaryopoiesis, including the presence of lymphoid small megakaryocytes, with the chromosomal monosomy or/and the rearrangement/amplification of C-erbB, were found in a few parents and siblings. These results were consistent with those of MDS, Fanconi Anemia (FA) and AL. The normal karyotype and SCD positive of BM cells and PB lymphocytes, and PB lymphocyte chromosomal fragility and unstability were found in most of patients' parents, while familial chromosomal monosomy of BM cells and PB lymphocyte chromosomal fragility were found in parents and siblings of familial leukemia patients. Based on the studies of a large family with 7 cases of acute erythroleukamia and relative myeloleukemias in three consecutive generations and a family with 3 CAA and 1 AML, the rearrangement of c-erbB might be inherited. The rearrangement/amplification of c-erbB and its PCR detected results could be the indicators of gene diagnosis of preleukemia and might be useful in genetic conselling of leukemias. The common origin of AL, MDS and AA was discussed.
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PMID:[Relationship between the occurrences of AL, MDS and AA and abnormal BM proliferation of patient's parents]. 975 8

The authors describe the case of a 24-year-old female patient with Fanconi's anaemia where they diagnosed spinocellular carcinoma of the oesophagus. At the same time they found skeletal abnormalities, caked kidney with pelvic dystopia and uterus unicornis. In patients with Fanconi's anaemia frequently acute leukaemia, liver tumours and spinocellular carcinoma are described. The knowledge of these facts makes early diagnosis of these associated diseases possible.
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PMID:[Spinocellular carcinoma in a patient with Fanconi's anemia]. 982 73

The Foundation for Growth Science in Japan has monitored the safety and efficacy of GH treatment in GH-deficient patients since 1975. Data were collected from more than 32,000 patients up to December 31, 1997. New leukemia was observed in 14 patients and myelodysplastic syndrome (MDS) in one patient. The types of leukemia were acute lymphocytic leukemia (n = 6; 40%), acute myelocytic leukemia or MDS (n = 7; 47%), and chronic myelocytic leukemia (n = 2; 13%). Leukemia developed in 9 patients during GH treatment and in 6 after the cessation of GH treatment. Six patients had known risk factors for leukemia, such as Fanconi's anemia and previous radiation or chemotherapy. Patient-years of GH therapy was defined as the time from the first dose of GH to the date of the last visit during GH therapy, and patient-years of risk was defined as the time from the first dose of GH to December 31, 1997. The incidence of leukemia of patient-years of GH therapy and patient-years of risk in GH-treated patients without risk factors was 3.0/100,000 and 3.9/100,000, respectively, a figure similar to the incidence in the general population aged 0-15 yr. We conclude that the incidence of leukemia in GH-treated patients without risk factors is not greater than that in the general population aged 0-15 yr, and a possible increased occurrence of leukemia with GH treatment appears to be limited to patients with risk factors.
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PMID:Recent status in the occurrence of leukemia in growth hormone-treated patients in Japan. GH Treatment Study Committee of the Foundation for Growth Science, Japan. 1037 94

By using R-banding karyotypic analysis technique, the bone marrow (BM) cells were performed in 223 hematopoietic malignacies and 105 diopathic throbocytopenic purpura (ITP), which served as control. The following results were obtained: (1) Nonrandom chromosome loss (NCL), such as, -11, -14, -21, etc, which were found in the affected members of leukemia families, were found in about 30% sporadic ANLL, MDS and about 50% ALL, espedislly in 100% (5/5) CLL, but not found in ITP (P < 0.001). These results indicated that the familial nonrandom chromosome loss were associated with leukomogenesis. (2) Because most of BM cells are hypodiploed and have the same kinds of NCL in each cases of CLL, which can develop into ALL, ANLL and also cancers, ALL BM hypo- and hyper-diploid and/or polyploid cells might be origin of hypodiploid cells. (3) 28% (6/21) of pediatric patients with AL, MDS, or FA (Fanconi Anemia) have one parent, who have up to 30% BM hypodiploid cells and similar kinds of NCL and also have the rearrangement of C-erbB and abnormal proliferation of BM. The NCL were found in the three consecutive generations of a family with 5 ALL among 10 members of third generation. It indicated that the familial NCL might be inherited and be coded by a unknown gene alteration, which might be related to leukomo and carcinogenesis, because there are genes or their candidates for leukemia in the chromosomes 11, 14 and 21. (4) Based on the works of my colleages and I, the model of leukomo and carcinogenesis was proposed and the relationship between chromosome monosomy, deletion, translocations and leukomogenesis were showed elswhere. The significance of monosomy 11, 14 and 21 etc. were discussed briefly.
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PMID:[Relationship between the familial nonrandom chromosome loss (NCL) and leukomogenesis]. 1037 57

Inherited bone marrow failure syndromes (BMFs) comprise at least one-fourth of children with aplastic anemia, and perhaps up to 10% of adults. The most common syndrome is Fanconi's anemia (FA), with more than 1,000 reported cases. FA is autosomal recessive, with birth defects in approximately 75% of patients. It is a DNA repair syndrome, diagnosed by finding chromosomal aberrations in cells treated with clastogenic agents. The major problems in FA are, in order, aplastic anemia, leukemia, and other cancers. There are at least five complementation groups; the gene for Group C has been cloned. Carrier identification and gene therapy are beginning in families at risk for FAC mutations. Dyskeratosis congenita (DC) is primarily X-linked (at Xq28), with autosomal recessive and dominant cases as well. Patients classically have reticulated hyperpigmented skin, dystrophic nails, and mucous membrane leukoplakia. approximately 50% develop aplastic anemia, sometimes prior to the DC phenotype, and approximately 10% develop cancer. Shwachman-Diamond syndrome consists of exocrine pancreatic insufficiency with neutropenia; approximately 25% develop aplastic anemia and 5%-10% develop leukemia. Amegakaryocytic thrombocytopenia presents in infancy, and often evolves into aplastic anemia and/or leukemia. Single cytopenias include Diamond-Blackfan anemia (DBA), which is inherited pure red cell aplasia; transient erythroblastopenia of childhood; Kostmann's syndrome (KS) or infantile genetic agranulocytosis, and thrombocytopenia with absent radii in which there is neonatal thrombocytopenia and absent radii. DBA and KS, particularly the latter treated with G-CSF, may develop leukemia, and solid tumors have been reported in DBA. Treatment for the various BMFs includes bone marrow transplantation, androgens, and hematopoietic cytokines such as G-CSF. These inherited syndromes thus include various combinations of marrow failure and premalignancy.
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PMID:Aplastic Anemia, Pediatric Aspects. 1038 17

Fanconi's anaemia (FA) is an autosomal recessive disorder characterized by progressive bone marrow failure that often evolves towards acute leukaemia. FA also belongs to a group of chromosome instability diseases. Because telomeres are directly involved in chromosomal stability and in cell proliferation capacity, we examined telomere metabolism in peripheral blood mononuclear cells (PBMC). Telomere length was significantly shorter in 54 FA patient samples, compared to 51 controls (P<0.0001). In addition, mean telomere terminal restriction fragment lengths (TRF) in nine heterozygous patient samples did not differ from those of controls. In 14 samples from FA patients with severe aplastic anaemia (SFA), telomere length was significantly shorter than in 22 samples of age-matched FA patients with moderate haematological abnormalities (NSFA) (P<0.001). However, no correlation was found between TRF length and the presence of bone marrow clonal abnormalities in 16 additional, separately analysed, patient samples. Sequential measurement of TRF in six FA patients showed an accelerated rate of telomere shortening. Accordingly, telomere shortening rate was inversely correlated with clinical status. Telomerase, the enzyme that counteracts telomere shortening, was 4.8-fold more active in 25 FA patients than in 15 age-matched healthy controls. A model for the FA disease process is proposed.
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PMID:Accelerated telomere shortening and telomerase activation in Fanconi's anaemia. 1055 97


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