Glucosylceramide Synthase Is a Novel Biomarker of Midostaurin-Induced Cytotoxicity in Non-Mutant FLT3 Positive Acute Myeloid Leukemia Cells

Objective: Glucosylceramide (GC) synthesized by glucosylceramide synthase (GCS) favors cell survival and proliferation in many cancers. However, it’s role Fms-like tyrosine kinase 3 (FLT3) non-mutant Acute Myeloid Leukemia (AML) pathogenesis is not clarified. Midostaurin, a multi-kinase inhibitor, clinically benefits FLT3-mutated AML, however, its clinical efficacy under-estimated FLT3 AML. This study aimed to investigate the of combination midostaurin with GCS inhibitor AML carrying wild-type underlying molecular mechanisms. Material Method: Cytotoxic cytostatic effects midostaurin, PDMP (GCS inhibitor) alone on THP1 cells were determined MTT assay flow cytometric propidium iodide (PI) staining, respectively. Calcusyn software was used calculate indexes (CIs). expression checked western blot. Results: Midostaurin downregulated GCS. Simultaneous inhibition resulted suppression as compared untreated control. Combinations showed synergistic cytotoxic (CI<1). Co-treatments increased cycle population at G2/M phase. Conclusion: Inhibition enhances midostaurin which could be novel therapeutic approach increase midostaurin’s limited usage clinic after detailed mechanistic studies.