Targeting integrated stress response with ISRIB combined with imatinib treatment attenuates RAS/RAF/MAPK and STAT5 signaling and eradicates chronic myeloid leukemia cells.

ABSTRACT: The integrated stress response (ISR) facilitates cellular adaptation to unfavorable conditions by reprogramming the cellular response. ISR activation was reported in neurological disorders and solid tumors; however, the function of ISR and its role as a possible therapeutic target in hematological malignancies still remain largely unexplored. Previously, we showed that the ISR is activated in chronic myeloid leukemia (CML) cells and correlates with blastic transformation and tyrosine kinase inhibitor (TKI) resistance. Moreover, the ISR was additionally activated in response to imatinib as a type of protective internal signaling. Here, we show that ISR inhibition combined with imatinib treatment sensitized and more effectively eradicated leukemic cells both in vitro and in vivo compared to

SUBMITTER: Dudka W 

PROVIDER: S-EPMC9719211 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature