CBP Modulates Sensitivity to Dasatinib in Pre-BCR⁺ Acute Lymphoblastic Leukemia.

ABSTRACT: Dasatinib is a multi-tyrosine kinase inhibitor approved for treatment of Ph⁺ acute lymphoblastic leukemia (ALL), but its efficacy is limited by resistance. Recent preclinical studies suggest that dasatinib may be a candidate therapy in additional ALL subtypes including pre-BCR⁺ ALL. Here we utilized shRNA library screening and global transcriptomic analysis to identify several novel genes and pathways that may enhance dasatinib efficacy or mitigate potential resistance in human pre-BCR⁺ ALL. Depletion of the transcriptional coactivator CBP increased dasatinib sensitivity by downregulating transcription of the pre-BCR signaling pathway previously associated with dasatinib sensitivity. Acquired resistance was due, in part, to upregulation of alternative pathw

SUBMITTER: Duque-Afonso J 

PROVIDER: S-EPMC6283070 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature