Drug-induced inhibition of phosphorylation of STAT5 overrides drug resistance in neoplastic mast cells.

ABSTRACT: Systemic mastocytosis (SM) is a mast cell (MC) neoplasm with complex pathology and a variable clinical course. In aggressive SM (ASM) and MC leukemia (MCL), responses to conventional drugs are poor and the prognosis is dismal. R763 is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT and FLT3. We examined the effects of R763 on proliferation and survival of neoplastic MC. R763 produced dose-dependent inhibition of proliferation in the human MC lines HMC-1.1 (IC₅₀ 5-50 nM), HMC-1.2 (IC₅₀ 1-10 nM), ROSA^{KIT WT} (IC₅₀ 1-10 nM), ROSA^{KIT D816V} (IC₅₀ 50-500 nM) and MCPV-1.1 (IC₅₀ 100-1000 nM). Moreover, R763 induced growth inhibition in primary neoplastic MC in patients with ASM and MCL. Gr

SUBMITTER: Peter B 

PROVIDER: S-EPMC6037300 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature