期刊
EXPERIMENTAL HEMATOLOGY
卷 43, 期 9, 页码 775-780出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.exphem.2015.04.013
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资金
- Canceropole Grand Ouest [AO-2009]
- Sport et Collection [AO-1-2008]
BCR-ABL induces an intrinsic genetic instability in chronic myeloid leukemia (CML). The protein breast cancer 1, early onset (BRCA1)-associated protein 1 (BAP1) is a deubiquitinase interacting with the DNA repair regulator BRCA1 and is frequently inactivated in many cancers. Here, we report that BAP1 mRNA and protein levels are downregulated in a BCR-ABL1-expressing hematopoietic cell line (UT-7/11). A decrease of BAP1 transcripts is also observed in newly diagnosed CML patients. Moreover, BAP1 protein levels are low or undetectable in CD34(+) cells from CML patients at diagnosis as compared with CD34(+) cells from normal donors. In addition, BRCA1 protein level is reduced in BCR-ABL1-expressing UT-7/11 cells. Finally, the enforced expression of BAP1 is associated with BRCA1 protein deubiquitination and restoration. These results demonstrate BAP1 as a major link with the BCR-ABL-induced downregulation of BRCA1 in CML. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.
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