Hoffmann L, Möller P, Pedersen-Bjergaard J, Waage A, Pedersen M, Hirsch F R
Laboratory for Cancer Genetics and Cytogenetics, Finsen Center, Rigshospitalet, Copenhagen, Denmark.
Ann Oncol. 1995 Oct;6(8):781-8. doi: 10.1093/oxfordjournals.annonc.a059316.
The development of therapy-related acute myeloid leukemia (t-AML) with balanced translocations to chromosome bands 11q23 and 21q22 has recently been significantly related to previous treatment with several cytostatic drugs poisoning DNA topoisomerase II. A similar association was suspected for other balanced chromosomal aberrations such as the t(15;17) characteristic of acute promyelocytic leukemia (APL).
Two cases of acute promyelocytic leukemia were observed following treatment for seminoma with etoposide, cisplatin, and bleomycin and treatment for breast cancer with 4-epi-doxorubicin and subsequent cyclophosphamide, methotrexate, and 5-fluorouracil followed by radiotherapy. Both cases presented a t(15;17) (q22;q12) and were examined for the characteristic chimeric rearrangement of the RAR alpha and PML genes observed in acute promyelocytic leukemia de-novo.
In both cases the characteristic chimeric rearrangement was demonstrated. Case no. 2 in addition to the t(15;17) showed an inversion of the long arm of a chromosome no. 5 and a del(7)(q22) in all abnormal mitoses studied. Despite these findings the patient obtained a complete morphological and cytogenetic remission of the leukemia following treatment with all-trans-retinoic acid.
Based on these two cases and a review of the literature it is concluded that the development of t-APL with the balanced translocation t(15;17) is related to previous treatment with cytostatic drugs targeting DNA topoisomerase II and that additional abnormalities of the long arms of chromosomes no. 5 and no. 7 do not interfere with the induction of remission with all-trans-retinoic acid.
与染色体带11q23和21q22发生平衡易位的治疗相关急性髓系白血病（t-AML）的发生，最近与先前使用多种抑制DNA拓扑异构酶II的细胞毒性药物治疗显著相关。对于其他平衡染色体畸变，如急性早幼粒细胞白血病（APL）的特征性t(15;17)，也怀疑存在类似关联。
观察到2例急性早幼粒细胞白血病患者，1例曾接受依托泊苷、顺铂和博来霉素治疗精原细胞瘤，另1例曾接受4-表阿霉素及随后的环磷酰胺、甲氨蝶呤和5-氟尿嘧啶治疗乳腺癌，之后接受放疗。2例均呈现t(15;17)(q22;q12)，并检测了急性早幼粒细胞白血病初发时观察到的RARα和PML基因特征性嵌合重排。
2例均证实存在特征性嵌合重排。病例2除t(15;17)外，在所有研究的异常有丝分裂中还显示5号染色体长臂倒位和7号染色体(7)(q22)缺失。尽管有这些发现，但该患者经全反式维甲酸治疗后白血病获得了完全形态学和细胞遗传学缓解。
基于这2例病例及文献复习得出结论，具有平衡易位t(15;17)的t-APL的发生与先前使用靶向DNA拓扑异构酶II的细胞毒性药物治疗有关，且5号和7号染色体长臂的其他异常并不干扰全反式维甲酸诱导缓解。
