Larson R A, LeBeau M M, Vardiman J W, Rowley J D
Department of Medicine, University of Chicago, Illinois 60637-1470, USA.
Environ Health Perspect. 1996 Dec;104 Suppl 6(Suppl 6):1303-7. doi: 10.1289/ehp.961041303.
One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation, has a myelodysplastic phase with trilineage involvement, and is characterized by abnormalities of the long arms of chromosomes 5 and/or 7. Response to treatment is poor, and allogenic bone marrow transplantation is recommended. Leukemia following treatment with agents that inhibit topoisomerase II, however, has a shorter latency, no preleukemic phase, a monoblastic, myelomonocytic, or myeloblastic phenotype, and balanced translocations, most commonly involving chromosome bands 11q23 or 21q22. The MLL gene at 11q23 or the AML1 gene at 21q22 are almost uniformly rearranged. MLL is involved with many fusion gene partners. Therapy-related acute lymphoblastic leukemia also occurs with 11q23 rearrangements. Therapy-related leukemias with 11q23 or 21q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts.
癌症治疗最严重的后果之一是引发第二种癌症，尤其是白血病。目前可以区分出几种不同类型的治疗相关白血病。经典的治疗相关髓系白血病通常在接触烷化剂和/或放疗后5至7年发生，有一个涉及三系的骨髓发育异常阶段，其特征是5号和/或7号染色体长臂异常。对治疗的反应较差，建议进行异基因骨髓移植。然而，用抑制拓扑异构酶II的药物治疗后发生的白血病潜伏期较短，没有白血病前期，具有单核细胞、粒单核细胞或粒细胞表型，以及平衡易位，最常见的是涉及11q23或21q22染色体带。11q23处的混合谱系白血病基因（MLL）或21q22处的急性髓系白血病1基因（AML1）几乎均发生重排。MLL与许多融合基因伙伴有关。治疗相关急性淋巴细胞白血病也会发生11q23重排。具有11q23或21q22重排、inv(16)或t(15;17)的治疗相关白血病对治疗的反应更好，临床病程与其原发性对应白血病相似。
