Targeting the Creatine Kinase Pathway in EVI1-Positive Acute Myeloid Leukemia

Purpose: Identify new targets in EVI1-Positive Acute Myeloid Leukemia Methods: Treatment with cyclocreatine of EVI1-driven AML cell lines TF-1, UT-7 and UCSD-AML1. Cyclocreatine was purchased from Sigma-Aldrich (Sigma). TF-1, UT-7 and UCSD-AML1 cells were treated in quadruplicate with either vehicle or 3 mM cyclocreatine for 24 hours. Total RNA was extracted and profiled by RNA sequencing (HiSeq, Illumina) at BioMicroCenter from Massachusetts Institute of Technology (Cambridge, MA, USA). Results: Alteration of arginine-creatine metabolism by the small-molecule cyclocreatine selectively decreased the viability, promoted cell cycle arrest and apoptosis of EVI1-positive AML cells. Conclusions: Targeting CKMT1 is a promising therapeutic strategy for the EVI1-driven AML subtype that is highly resistant to current treatment regimens. mRNA profiles for the EVI1-driven AML cell lines TF-1, UT-7 and UCSD-AML1 treated with either 3mM cyclocreatine for 24 hours or with vehicle were generated in quadruplicate by RNA sequencing (HiSeq, Illumina) at the BioMicroCenter from Massachusetts Institute of Technology (Cambridge, MA, USA).