ArticleBlood advances2023
EVI1 exerts distinct roles in AML via ERG and cyclin D1 promoting a chemoresistant and immune-suppressive environment.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.European journal of haematology · 2026Review
- MECOM promotes leukemia progression and inhibits mast cell differentiation through functional competition with GATA2.Leukemia · 2026Article
- Genome-wide screening identifies ZFP91 as a key regulator of EVI1 in myeloid leukemia.Oncogene · 2026Article
- CCAAT-enhancer binding protein delta functions as a tumor suppressor gene in acute myeloid leukemia.Neoplasia (New York, N.Y.) · 2026Article
- BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML.Leukemia · 2026Article
- Thrombopoietin increases susceptibility for EVI1 + KMT2A-MLLT3-driven AML expressing stem cell genes linked to poor outcome.Nature communications · 2025Article
- Identification of an Ara-C resistance-related gene risk score and the role of S100A4 in AML via NR6A1-dependent activation and p53 regulation.Frontiers in pharmacology · 2025Article
- Nicotinamide mononucleotide protects STAT1 from oxidative stress-induced degradation to prevent colorectal tumorigenesis.MedComm · 2024Article
- EVI1-mediated Programming of Normal and Malignant Hematopoiesis.HemaSphere · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant expression of ecotropic viral integration site-1 (EVI1+) is associated with very poor outcomes in acute myeloid leukemia (AML), mechanisms of which are only partially understood. Using the green fluorescent protein reporter system to monitor EVI1 promoter activity, we demonstrated that Evi1high KMT2A-MLLT1-transformed AML cells possess distinct features from Evi1low cells: the potential for aggressive disease independent of stem cell activity and resistance to cytotoxic chemotherapy, along with the consistent gene expression profiles. RNA sequencing and chromatin immunoprecipitation sequencing in EVI1-transformed AML cells and normal hematopoietic cells combined with functional screening by cell proliferation-related short hairpin RNAs revealed that the erythroblast transformation-specific transcription factor ERG (E26 transformation-specific [ETS]-related gene) and cyclin D1 were downstream targets and therapeutic vulnerabilities of EVI1+ AML. Silencing Erg in murine EVI1+ AML models severely impaired cell proliferation, chemoresistance, and leukemogenic capacity. Cyclin D1 is also requisite for efficient EVI1-AML development, associated with gene expression profiles related to chemokine production and interferon signature, and T- and natural killer-cell exhaustion phenotype, depending on the interferon gamma (IFN-γ)/STAT1 pathway but not on CDK4/CDK6. Inhibiting the IFN-γ/STAT1 pathway alleviated immune exhaustion and impaired EVI1-AML development. Overexpression of EVI1 and cyclin D1 was associated with IFN-γ signature and increased expression of chemokines, with increased exhaustion molecules in T cells also in human AML data sets. These data collectively suggest that ERG and cyclin D1 play pivotal roles in the biology of EVI1+ AML, where ERG contributes to aggressive disease nature and chemoresistance, and cyclin D1 leads to IFN-γ signature and exhausted T-cell phenotypes, which could potentially be targeted.
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