Paquette Ronald L, Nicoll John, Chalukya Meenal, Elashoff David, Shah Neil P, Sawyers Charles, Spiteri Elizabeth, Nanjangud Gouri, Rao P Nagesh
UCLA Department of Medicine, Los Angeles, CA, USA.
Cancer Genet. 2011 Jul;204(7):392-7. doi: 10.1016/j.cancergen.2011.06.002.
Clinical variables associated with ecotropic viral integration site 1 (EVI1) translocations were evaluated in 42 consecutive chronic myeloid leukemia (CML) patients in myeloid blast crisis (MBC). Translocations were confirmed with fluorescence in situ hybridization, and Western blot analysis demonstrated EVI1 expression. Translocations of EVI1 were present in 3 of 24 (12%) patients whose disease evolved MBC before tyrosine kinase inhibitor (TKI) exposure, and 7 of 18 (39%) patients who had received one or more TKIs. Univariate analysis showed that prior TKI therapy was the only clinical variable that was significantly associated with EVI1 translocation (P = 0.047). TKI-resistant BCR-ABL1 mutations were present in 71% of MBC patients with EVI1 translocations at the time of disease progression. These observations suggest that EVI1 overexpression collaborates with BCR-ABL1 in the evolution of TKI-resistant MBC. Inhibition of c-ABL kinase-mediated DNA double-strand repair by TKIs may predispose to EVI1 translocation in this setting.
在42例连续的处于髓系原始细胞危象（MBC）的慢性髓性白血病（CML）患者中，评估了与嗜异性病毒整合位点1（EVI1）易位相关的临床变量。通过荧光原位杂交确认易位，蛋白质免疫印迹分析显示EVI1表达。在24例在酪氨酸激酶抑制剂（TKI）暴露前疾病进展为MBC的患者中有3例（12%）存在EVI1易位，在18例接受过一种或多种TKI治疗的患者中有7例（39%）存在EVI1易位。单因素分析显示，既往TKI治疗是唯一与EVI1易位显著相关的临床变量（P = 0.047）。在疾病进展时，71%的伴有EVI1易位的MBC患者存在TKI耐药的BCR-ABL1突变。这些观察结果表明，EVI1过表达在TKI耐药的MBC演变过程中与BCR-ABL1协同作用。在这种情况下，TKI对c-ABL激酶介导的DNA双链修复的抑制可能易导致EVI1易位。
