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

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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.