CDK4/CDK6 inhibition as a novel strategy to suppress the growth and survival of BCR-ABL1^T315I+ clones in TKI-resistant CML.

ABSTRACT:

Purpose

Ponatinib is the only approved tyrosine kinase inhibitor (TKI) suppressing BCR-ABL1^T315I-mutated cells in chronic myeloid leukemia (CML). However, due to side effects and resistance, BCR-ABL1^T315I-mutated CML remains a clinical challenge. Hydroxyurea (HU) has been used for cytoreduction in CML for decades. We found that HU suppresses or even eliminates BCR-ABL1^T315I+ sub-clones in heavily pretreated CML patients. Based on this observation, we investigated the effects of HU on TKI-resistant CML cells in vitro.

Methods

Viability, apoptosis and proliferation of drug-exposed primary CML cells and BCR-ABL1+ cell lines were examined by flow cytometry and ³H-thymidine-uptake. Expression of drug targets was analyzed by qPCR and Wes

SUBMITTER: Schneeweiss-Gleixner M 

PROVIDER: S-EPMC6921367 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature