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Genome-Wide CRISPR-Cas9 screening identifies BRAF inhibitor as a sensitizer of dasatinib in treating T-acute lymphoblastic leukemia

ABSTRACT: T-cell acute lymphoblastic leukemia is an aggressive hematologic tumor with fewer treatment strategies. Dasatinib, an FDA-approved tyrosine kinase inhibitor applied in chronic myelogenous leukemia and acute lymphoblastic leukemia with Philadelphia chromosome-positive has been utilized in T-ALL for cure but the clinical outcomes are not satisfied, calling for further investigation on the mechanism and potential combinations to overcome resistance. In this study, we performed a genome-wide CRISPR-Cas9 screening and identified the MAPK pathway as an essential regulator of sensitivity to dasatinib. Then we confirmed that the inhibition of the MAPK pathway by dabrafenib could sensitize T-ALL cells to dasatinib in vitro and reveal the underlying mechanism by RNA sequencing. Together, we put forward a promising combining strategy for T-ALL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE218078 | GEO | 2025/06/01

REPOSITORIES: GEO

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