ArticleNature medicine2017
The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Targeting Mitochondrial Oxidative Phosphorylation Eradicates Acute Myeloid Leukemic Stem Cells.Frontiers in oncology · 2022Pooled it
- Multi-omics analysis reveals LARP1 as a key integrator of translation and metabolism in AML.Oncogenesis · 2026Article
- Creatine kinase regulates energy metabolism and growth of trophoblasts.bioRxiv : the preprint server for biology · 2026Article
- Review
- The oncogenic role of ecotropic viral integration site 1 in hematological malignancies: mechanisms of activation and leukemogenesis.Frontiers in immunology · 2026Review
- Article
- Creatine kinase imaging (CKI) for in vivo whole-brain mapping of creatine kinase reaction kinetics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Streptococcus gallolyticus supernatant induces M2 macrophage polarization and activates IL-17 F signaling in colorectal tumorigenesis.Gut pathogens · 2025Article
- SIRT5 inhibition impairs mitochondrial metabolism and enhances venetoclax-induced elimination of acute myeloid leukemia cells.Leukemia · 2025Article
- PRC2-mediated apoptosis evasion is a therapeutic target of MDS/AML harboring inv(3)/t(3;3) and monosomy 7.HemaSphere · 2025Article
- Structural basis for substrate binding, catalysis, and inhibition of cancer target mitochondrial creatine kinase by a covalent inhibitor.Structure (London, England : 1993) · 2025Article
- MTHFD2 promotes osteoclastogenesis and bone loss in rheumatoid arthritis by enhancing CKMT1-mediated oxidative phosphorylation.BMC medicine · 2025Article
- Targeting Creatine and Creatine Kinase in Cancer: Exploring Potential Therapeutic Strategies.Current drug targets · 2025Review
- Hydrogel models of pancreatic adenocarcinoma to study cell mechanosensing.Biophysical reviews · 2024Review
- Spatial metabolomics highlights metabolic reprogramming in acute myeloid leukemia mice through creatine pathway.Acta pharmaceutica Sinica. B · 2024Article
- CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Aberrant ecotropic viral integration site-1 (EVI-1) and myocyte enhancer factor 2 C gene (MEF2C) in adult acute myeloid leukemia are associated with adverse t (9:22) & 11q23 rearrangements.Annals of hematology · 2024Article
- Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML.Nature communications · 2024Article
- Context-dependent roles for ubiquitous mitochondrial creatine kinase CKMT1 in breast cancer progression.Cell reports · 2024Article
- Enhancing Leukemia Treatment: The Role of Combined Therapies Based on Amino Acid Starvation.Cancers · 2024Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 10 institutions in 2 countries.
Funding
Abstract
Expression of the MECOM (also known as EVI1) proto-oncogene is deregulated by chromosomal translocations in some cases of acute myeloid leukemia (AML) and is associated with poor clinical outcome. Here, through transcriptomic and metabolomic profiling of hematopoietic cells, we reveal that EVI1 overexpression alters cellular metabolism. A screen using pooled short hairpin RNAs (shRNAs) identified the ATP-buffering, mitochondrial creatine kinase CKMT1 as necessary for survival of EVI1-expressing cells in subjects with EVI1-positive AML. EVI1 promotes CKMT1 expression by repressing the myeloid differentiation regulator RUNX1. Suppression of arginine-creatine metabolism by CKMT1-directed shRNAs or by the small molecule cyclocreatine selectively decreased the viability, promoted the cell cycle arrest and apoptosis of human EVI1-positive cell lines, and prolonged survival in both orthotopic xenograft models and mouse models of primary AML. CKMT1 inhibition altered mitochondrial respiration and ATP production, an effect that was abrogated by phosphocreatine-mediated reactivation of the arginine-creatine pathway. Targeting CKMT1 is thus a promising therapeutic strategy for this EVI1-driven AML subtype that is highly resistant to current treatment regimens.
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Registered trials
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