Creatine kinase pathway inhibition alters GSK3 and WNT signaling in EVI1-positive AML.
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ABSTRACT:
SUBMITTER: Benajiba L
PROVIDER: S-EPMC6596421 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
Publications
Creatine kinase pathway inhibition alters GSK3 and WNT signaling in EVI1-positive AML.
Benajiba Lina L Alexe Gabriela G Su Angela A Raffoux Emmanuel E Soulier Jean J Hemann Michael T MT Hermine Olivier O Itzykson Raphael R Stegmaier Kimberly K Puissant Alexandre A
Leukemia 20181102 3
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Project description: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.
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