SRSF1 mediates cytokine-induced impaired imatinib sensitivity in chronic myeloid leukemia.

ABSTRACT: Patients with chronic myeloid leukemia (CML) who are treated with tyrosine kinase inhibitors (TKIs) experience significant heterogeneity regarding depth and speed of responses. Factors intrinsic and extrinsic to CML cells contribute to response heterogeneity and TKI resistance. Among extrinsic factors, cytokine-mediated TKI resistance has been demonstrated in CML progenitors, but the underlying mechanisms remain obscure. Using RNA-sequencing, we identified differentially expressed splicing factors in primary CD34⁺ chronic phase (CP) CML progenitors and controls. We found SRSF1 expression to be increased as a result of both BCR-ABL1- and cytokine-mediated signaling. SRSF1 overexpression conferred cytokine independence to untransformed hematopoietic cells and impaired imatinib sen

SUBMITTER: Sinnakannu JR 

PROVIDER: S-EPMC7682023 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature