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Expression data from a reversible dasatinib-resistant state in long-term dasatinib-treated c-KIT-mutated Kasumi-1 cell line

ABSTRACT: Long-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored. We used gene expression profiling to examine reversal of dasatinib-resistance at the molecular/expression level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE39073 | GEO | 2013/11/27

SECONDARY ACCESSION(S): PRJNA169900

REPOSITORIES: GEO

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Expression data from a reversible dasatinib-resistant state in long-term dasatinib-treated c-KIT-mutated Kasumi-1 cell line

Project description:Long-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored. We used gene expression profiling to examine reversal of dasatinib-resistance at the molecular/expression level. Kasumi-1 cells were either treated with dasatinib for 12 weeks (R48) or left untreated (K). Subsequently, dasatinib was withdrawn from R48 cells for 1 week (PR48). RNA was extracted from R48 and K cells and hybridized on Affymetrix microarrays after 12 weeks and PR48 after a total time span of 13 weeks.

2013-11-27 | E-GEOD-39073 | biostudies-arrayexpress

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Project description:Natural Killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in the research and clinical trials. Clinical observations witnessed the improvement of patients’ NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug against CML and Ph+ ALL. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By coculturing NK cells with dasatinib to test the cell counts and target cell killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK killing tumor cells. RNA-seq analysis further supported this finding, uncovering several proliferating and cytotoxic pathways were responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

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