Journal
CANCER CELL
Volume 16, Issue 3, Pages 232-245Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2009.07.030
Keywords
-
Categories
Funding
- NIH/NCI [R01CA137060, R01CA139032]
- Leukemia and Lymphoma Society
- V Foundation for Cancer Research
- Deutsche Forschungsgemeinschaft (German Science Foundation) [MU1616/5-1]
- Kenneth T. and Eileen L. Norris Foundation
Ask authors/readers for more resources
Chronic myeloid leukemia (CIVIL) 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 CIVIL cells express the B cell-specific mutator enzyme AID. We demonstrate that AID expression in CIVIL 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available