Abnormalities of the retinoblastoma gene in the pathogenesis of acute leukemia.
The retinoblastoma-susceptibility (Rb) gene is an antioncogene that is frequently altered in retinoblastomas, sarcomas, and some epithelial tumors. We examined the structure of the Rb gene by Southern blotting in 215 cases of leukemias and lymphomas of diverse phenotype and in 15 leukemic cell lines. In selected cases Rb protein expression was examined with specific monoclonal antibodies. Structural abnormalities of the Rb gene with absent protein expression were frequent in all types of human acute leukemia, but were particularly common (27% incidence) in M4 and M5 myeloid leukemia with monocytic differentiation and in Philadelphia chromosome (Ph1)-positive leukemia of lymphoid phenotype (11% to 29% incidence). Changes in Rb were observed early in the transition to acute leukemia in cases of myelodysplastic syndrome and in the accelerated phase of chronic myelocytic leukemia in transition to blast crisis. In one case, molecular changes in Rb could be correlated with leukemia remission and relapse. We conclude that the Rb antioncogene is commonly involved in the evolution of human acute leukemias, particularly in those of a monocytic phenotype and in lymphoid leukemia in which there is an antecedent alteration of the Ph1 chromosome.
Department of Medicine, UCLA.
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Ahuja
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Jat
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Foti
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Bar-Eli
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Cline
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D001752:Blast Crisis / Q000235:genetics; D015139:Blotting, Southern; D002648:Child; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression; D016161:Genes, Retinoblastoma / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007938:Leukemia / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics; D010677:Philadelphia Chromosome; D012150:Polymorphism, Restriction Fragment Length; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm