[Secondary leukemias: their clinical features, incidence among populations at risk, mechanisms and new strategy for prediction].
Clinically distinct features in both alkylating agents--and topoisomerase II (topo II)-induced secondary leukemias (SL) are reviewed with special reference to the increasing frequencies observed in relation to advances in modern cancer chemotherapy. Topo II interacts with, and then stabilizes the cleavable complex that ultimately results in double strand breaks. In patients with SL, breakpoints in MLL gene are clustered within SARs of 3' bcr. However, mechanisms by which the former type of SL is caused remain to be elucidated. Since alkylating agents often induce profound marrow dysplasia, long-lived lesions induced on hematopoietic stem cells are of potential relevance to the development of SL. This process may be partially demonstrated by the variety of mitotic modifications found in MDS. Recently, the association has been investigated between certain enzyme polymorphisms related to activation or detoxification of anticancer agents and SL. These studies have potential importance, since individuals with a certain genotype may be at increased risk for SL.
Abe
T
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Dept. of Hygiene, Kyoto Prefectural University of Medicine, Japan.
D000782:Aneuploidy; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D004247:DNA / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D005544:Forecasting; D006801:Humans; D007938:Leukemia / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D011110:Polymorphism, Genetic; D012306:Risk
D018906:Antineoplastic Agents, Alkylating; D004247:DNA; D004250:DNA Topoisomerases, Type II