Inhibition of CPT1a as a prognostic marker can synergistically enhance the antileukemic activity of ABT199

Abstract Background Fatty acid oxidation (FAO) provides an important source of energy to promote the growth leukemia cells. Carnitine palmitoyltransferase 1a(CPT1a), a rate-limiting enzyme essential step FAO, can facilitate cancer metabolic adaptation. Previous reports demonstrated that CPT1a acts as potential molecular target in solid tumors and hematologic disease. However, no systematic study was conducted explore prognostic value expression possible treatment strategies with inhibitor on acute myeloid (AML). Methods The 325 cytogenetically normal AML (CN-AML) patients evaluated using RT-PCR. combination effects ST1326 ABT199 were studied cells primary patients. MTS used measure cell proliferation rate. Annexin V/propidium iodide staining flow cytometry analysis apoptosis Western blot Mcl-1. RNAseq GC-TOFMS for genomic analysis. Results In this study, we found high (n = 245) had relatively short overall survival (P 0.01) compared low group 80). parallel, downregulation inhibits We also interactive patients, several genes pathways related aberrant CPT1a. Moreover, sentitized BCL-2 CPT1a-selective combined strong synergistic effect induce patient blasts first time. underlying mechanism might be pGSK3? pERK expression, leading Conclusion Our indicates overexpression predicts poor clinical outcome AML. Bcl-2 showed inhibitory