Andersen M K, Johansson B, Larsen S O, Pedersen-Bjergaard J
Finsen Center, Rigshospitalet-University Hospital, Department of Medical Statistics, Copenhagen, Denmark.
Haematologica. 1998 Jun;83(6):483-8.
In therapy-related myelodysplasia (t-MDS) or acute myeloid leukemia (t-AML) balanced chromosome aberrations to bands 11q23 and 21q22 have been significantly related to previous chemotherapy with DNA topoisomerase II inhibitors. The purpose of the present study was to evaluate to what extent other balanced chromosome aberrations show the same association, and to evaluate a possible relationship to patient age and subgroups of drugs.
All previously published cases of t-MDS and t-AML with any type of balanced aberration identified from Felix Mitelman's Catalog of Chromosome Aberrations in Cancer were analyzed for age and type of previous therapy, and the results were evaluated in univariate and multivariate analyses.
A total of 422 cases were recorded, 328 had previously received well specified types of chemotherapy; 254 presented one out of five characteristic balanced aberrations, whereas 168 cases presented different uncharacteristic balanced aberrations. In univariate analysis cases with translocations to 11q23 had most often received DNA topoisomerase II inhibitors, whereas patients with the uncharacteristic balanced rearrangements most often had received alkylating agents (p < 0.00000001). Inv(16), t(15;17), and t(9;22) were likewise significantly associated with previous therapy with DNA topoisomerase II inhibitors and to almost the same extent as translocations to 21q22. Patients with translocations to 11q23 were significantly younger as compared to all other groups of patients. Translocations to 11q23 predominated following therapy with epipodophyllotoxins, whereas patients with translocations to 21q22, inv(16), t(15;17), and t(9;22) most often had received anthracyclines. In a multivariate analysis taking age into consideration, however, these drug-specific associations were no longer significant.
Specific balanced chromosome aberrations in t-MDS and t-AML involving chromosome bands 11q23 and 21q22, inv(16), t(15;17), and t(9;22) are all significantly associated with previous therapy with DNA topoisomerase II inhibitors, as compared to the uncharacteristic balanced aberrations most commonly observed after therapy with alkylating agents. Younger age and not a specific type of DNA topoisomerase II inhibitor seems to predispose specifically to development of t-MDS and t-AML with translocations to chromosome band 11q23.
在治疗相关的骨髓增生异常综合征（t-MDS）或急性髓系白血病（t-AML）中，11q23和21q22带的平衡染色体畸变与先前使用DNA拓扑异构酶II抑制剂进行的化疗显著相关。本研究的目的是评估其他平衡染色体畸变在多大程度上显示出相同的关联，并评估其与患者年龄和药物亚组之间的可能关系。
对从费利克斯·米特尔曼的《癌症染色体畸变目录》中识别出的所有先前发表的伴有任何类型平衡畸变的t-MDS和t-AML病例进行年龄和先前治疗类型分析，并在单变量和多变量分析中评估结果。
共记录422例病例，其中328例先前接受了明确的化疗类型；254例呈现出五种特征性平衡畸变中的一种，而168例呈现不同的非特征性平衡畸变。在单变量分析中，11q23易位的病例最常接受DNA拓扑异构酶II抑制剂治疗，而非特征性平衡重排的患者最常接受烷化剂治疗（p<0.00000001）。inv(16)、t(15;17)和t(9;22)同样与先前使用DNA拓扑异构酶II抑制剂的治疗显著相关，且程度与21q22易位几乎相同。与所有其他患者组相比，11q23易位的患者明显更年轻。11q23易位在使用表鬼臼毒素治疗后占主导，而21q22易位、inv(16)、t(15;17)和t(9;22)的患者最常接受蒽环类药物治疗。然而，在考虑年龄的多变量分析中，这些药物特异性关联不再显著。
与烷化剂治疗后最常见的非特征性平衡畸变相比，t-MDS和t-AML中涉及11q23和21q22染色体带、inv(16)、t(15;17)和t(9;22)的特定平衡染色体畸变均与先前使用DNA拓扑异构酶II抑制剂的治疗显著相关。年龄较小而非特定类型的DNA拓扑异构酶II抑制剂似乎特别易患伴有11q23染色体带易位的t-MDS和t-AML。
