Dissing M, Le Beau M M, Pedersen-Bjergaard J
Laboratory for Cancer Genetics and Cytogenetics, The Finsen Center, Rigshospitalet, Copenhagen, Denmark.
J Clin Oncol. 1998 May;16(5):1890-6. doi: 10.1200/JCO.1998.16.5.1890.
To evaluate the frequency of inversion of chromosome 16 (inv[16]) and the type of rearrangement of the CBFB and MYH11 genes in therapy-related acute myeloid leukemia (t-AML) and to evaluate a possible relationship to specific types of previous chemotherapy.
Cytogenetic studies were performed in 180 consecutive patients with therapy-related myelodysplasia (t-MDS) or t-AML in Copenhagen and in 270 consecutive patients in Chicago. Leukemic cells were available for studies of the molecular biology in 72 patients, including four with inv(16).
An inv(16)(p13q22) was observed in only two of 180 cases of t-MDS and t-AML in Copenhagen and in only four of 270 cases of t-MDS and t-AML in Chicago. Four patients with t-AML and inv(16) previously had received combination chemotherapy, which included an alkylating agent, and in two a DNA topoisomerase II inhibitor was included (mitoxantrone and etoposide). One patient had received paclitaxel followed by etoposide and one patient had received radiotherapy only. One patient, previously treated with mitoxantrone and cyclophosphamide for breast cancer, presented a new and, to our knowledge not previously reported, type of fusion transcript, with breakpoint at nt 399 of the CBFB gene and at nt 2134 of the MYH11 gene. Two patients previously treated with alkylating agents both presented the less common type D transcript, whereas the most common A transcript, observed in 80% of acute myeloid leukemia (AML) de novo with inv(16), only was observed in the patient treated with paclitaxel and etoposide for leiomyosarcoma. Bone marrow or blood cells from 68 patients with t-MDS and t-AML without an inv(16) all were found to be negative for chimeric rearrangement between the CBFB gene and the MYH11 gene.
The present study and a review of the literature shows that inv(16) is an uncommon aberration in t-AML and, like balanced translocations to chromosome bands 11q23 and 21q22 and the t(15;17), often is associated with prior chemotherapy with DNA topoisomerase II inhibitors. Breakpoints within the MYH11 gene may vary between t-AML and AML de novo.
评估治疗相关急性髓系白血病（t-AML）中16号染色体倒位（inv[16]）的频率以及CBFB和MYH11基因的重排类型，并评估其与既往特定类型化疗之间的可能关系。
对哥本哈根的180例连续治疗相关骨髓增生异常综合征（t-MDS）或t-AML患者以及芝加哥的270例连续患者进行了细胞遗传学研究。72例患者的白血病细胞可用于分子生物学研究，其中4例存在inv(16)。
在哥本哈根的180例t-MDS和t-AML病例中仅观察到2例inv(16)(p13q22)，在芝加哥的270例t-MDS和t-AML病例中仅观察到4例。4例t-AML且伴有inv(16)的患者此前接受过联合化疗，其中包括一种烷化剂，2例还使用了DNA拓扑异构酶II抑制剂（米托蒽醌和依托泊苷）。1例患者先接受了紫杉醇治疗，随后接受依托泊苷治疗，1例患者仅接受了放疗。1例先前因乳腺癌接受米托蒽醌和环磷酰胺治疗的患者出现了一种新的、据我们所知此前未报道过的融合转录本类型，其断点位于CBFB基因的第399位核苷酸和MYH11基因的第2134位核苷酸处。2例先前接受烷化剂治疗的患者均出现了较罕见的D型转录本，而在80%的新发inv(16)急性髓系白血病（AML）中观察到的最常见的A型转录本，仅在1例因平滑肌肉瘤接受紫杉醇和依托泊苷治疗的患者中出现。68例无inv(16)的t-MDS和t-AML患者的骨髓或血细胞中，CBFB基因与MYH11基因之间的嵌合重排均为阴性。
本研究及文献综述表明，inv(16)在t-AML中是一种罕见的异常，与11q23和21q22染色体带的平衡易位以及t(15;17)一样，常与既往使用DNA拓扑异构酶II抑制剂的化疗相关。MYH11基因内的断点在t-AML和新发AML之间可能有所不同。
