Combined targeting of STAT3 and STAT5: a novel approach to overcome drug resistance in chronic myeloid leukemia.

ABSTRACT: In chronic myeloid leukemia, resistance against BCR-ABL1 tyrosine kinase inhibitors can develop because of BCR-ABL1 mutations, activation of additional pro-oncogenic pathways, and stem cell resistance. Drug combinations covering a broad range of targets may overcome resistance. CDDO-Me (bardoxolone methyl) is a drug that inhibits the survival of leukemic cells by targeting different pro-survival molecules, including STAT3. We found that CDDO-Me inhibits proliferation and survival of tyrosine kinase inhibitor-resistant BCR-ABL1⁺ cell lines and primary leukemic cells, including cells harboring BCR-ABL1^T315I or T315I⁺ compound mutations. Furthermore, CDDO-Me was found to block growth and survival of CD34⁺/CD38^- leukem

SUBMITTER: Gleixner KV 

PROVIDER: S-EPMC5685220 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature