Study of the mechanism of apoptosis and drug resistance in leukemic cells

伊马替尼是一种抗慢性粒细胞白血病（CML）的分子靶向药物，可诱导白血病细胞凋亡。Bach 2是一种B细胞特异性转录因子和促凋亡因子，在CML中被伊马替尼上调。为了研究伊马替尼通过Bach2诱导CML细胞凋亡的机制，我们分析了Bach2的定位和动力学。我们发现Bach 2在氧化应激时从细胞质迁移到细胞核，并在PML小体周围形成核灶。Bach 2选择性抑制与PML体相关的转录活性。此外，Bach 2需要蛋白质修饰以实现PML体的表达。由于PML是一种已知的促凋亡因子，因此这些结果表明，Bach 2可能通过伊马替尼治疗后CML细胞中与PML体相关的基因的转录抑制来诱导凋亡。

Imatinib is a molecular targeting drug against chronic myelocytic leukemia (CML), and induces apoptosis of leukemic cells. Bach2, a B cell specific transcription factor and a proapoptotic factor, is upregulated by imatinib in CML. To study the mechanism of the induction of apoptosis by imatinib via Bach2 in CML cells, we analyzed the localization and dynamics of Bach2. We found that Bach2 relocated from cytoplasm into cell nucleus and forms nuclear foci around PML body upon oxidative stress. Bach2 selectively repressed transcriptional activity associated with PML body. Furthermore, Bach2 required protein modification for the envelopment of PML body. Since PML is a known pro-apoptotic factor, these results suggest that Bach2 might induce apoptosis through the transcription repression of genes associated with PML body in CML cells after treatment with imatinib.