| First Author | Klemm L | Year | 2009 |
| Journal | Cancer Cell | Volume | 16 |
| Issue | 3 | Pages | 232-45 |
| PubMed ID | 19732723 | Mgi Jnum | J:152377 |
| Mgi Id | MGI:4358624 | Doi | 10.1016/j.ccr.2009.07.030 |
| Citation | Klemm L, et al. (2009) The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia. Cancer Cell 16(3):232-45 |
| abstractText | Chronic myeloid leukemia (CML) is induced by BCR-ABL1 and can be effectively treated for many years with Imatinib until leukemia cells acquire drug resistance through BCR-ABL1 mutations and progress into fatal B lymphoid blast crisis (LBC). Despite its clinical significance, the mechanism of progression into LBC is unknown. Here, we show that LBC but not CML cells express the B cell-specific mutator enzyme AID. We demonstrate that AID expression in CML cells promotes overall genetic instability by hypermutation of tumor suppressor and DNA repair genes. Importantly, our data uncover a causative role of AID activity in the acquisition of BCR-ABL1 mutations leading to Imatinib resistance, thus providing a rationale for the rapid development of drug resistance and blast crisis progression. |
