KIT^low Cells Mediate Imatinib Resistance in Gastrointestinal Stromal Tumor.

ABSTRACT: Gastrointestinal stromal tumor (GIST) is commonly driven by oncogenic KIT mutations that are effectively targeted by imatinib (IM), a tyrosine kinase inhibitor (TKI). However, IM does not cure GIST, and adjuvant therapy only delays recurrence in high-risk tumors. We hypothesized that GIST contains cells with primary IM resistance that may represent a reservoir for disease persistence. Here, we report a subpopulation of CD34⁺KIT^low human GIST cells that have intrinsic IM resistance. These cells possess cancer stem cell-like expression profiles and behavior, including self-renewal and differentiation into CD34⁺KIT^high progeny that are sensitive to IM treatment. We also found that TKI treatment of GIST cell lines led to induction of stem cell

SUBMITTER: Banerjee S 

PROVIDER: S-EPMC8492542 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature