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    GENE:

    MECOM (MDS1 And EVI1 Complex Locus)

    i
    Other names: MECOM, MDS1 And EVI1 Complex Locus, PRDM3, Ecotropic Virus Integration Site 1 Protein Homolog, Myelodysplasia Syndrome-Associated Protein 1, Histone-Lysine N-Methyltransferase MECOM, PR Domain 3, MDS1-EVI1, KMT8E, EVI1, MDS1, MDS1 And EVI1 Complex Locus Protein EVI1, MDS1 And EVI1 Complex Locus Protein MDS1, MDS1 And EVI1 Complex Locus Protein, Ecotropic Viral Integration Site 1, Myelodysplasia Syndrome 1 Protein, Myelodysplasia Syndrome 1, AML1-EVI-1 Fusion Protein, Zinc Finger Protein Evi1, Oncogene EVI1, AML1-EVI-1, RUSAT2, EVI-1
    1d
    Automated Total Marrow and Lymphoid Irradiation for Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov)
    P2, N=30, Not yet recruiting, Stanford University
    New P2 trial
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    TP53 (Tumor protein P53) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • MECOM (MDS1 And EVI1 Complex Locus) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
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    TP53 mutation
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    cyclophosphamide • fludarabine IV
    6d
    AKT inhibitor capivasertib reverses EVI1-driven resistance to venetoclax in acute myeloid leukaemia. (PubMed, Br J Haematol)
    Importantly, cotreatment with venetoclax and the clinically available AKT inhibitor capivasertib effectively restored sensitivity in both cell lines and patient-derived primary AML samples with high EVI1 expression. Overall, our findings reveal a novel molecular mechanism underlying EVI1-mediated venetoclax resistance through PI3K/AKT-driven MCL-1 stabilization and suggest a combination strategy involving AKT inhibition as a promising approach for overcoming therapeutic resistance in this high-risk AML subset.
    Journal
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    MCL1 (Myeloid cell leukemia 1) • MECOM (MDS1 And EVI1 Complex Locus)
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    Venclexta (venetoclax) • Truqap (capivasertib)
    8d
    Phase1b/2 Trial Of AZA + APG1252 In Patients With High-Risk AML (clinicaltrials.gov)
    P1/2, N=52, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Sep 2026 --> May 2026
    Enrollment open • Trial initiation date
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    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • MECOM (MDS1 And EVI1 Complex Locus)
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    pelcitoclax (APG-1252)
    9d
    Cell Line-Specific In Vitro Effects of Boric Acid and Meis1i-2 in Leukemia Cells: Apoptosis, Cell-Cycle Modulation, and Fixed-Dose Interaction. (PubMed, Cell Biol Int)
    Therefore, under the current experimental conditions, the combination demonstrates concentration-specific antileukemic activity rather than pharmacological interaction. Future studies using expanded sub-IC50 dose matrices, protein-level and functional validation, and in vivo models are required.
    Preclinical • Journal
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    MECOM (MDS1 And EVI1 Complex Locus) • ANXA5 (Annexin A5)
    11d
    Optical Genome Mapping in Myeloid Neoplasms. (PubMed, Hum Pathol)
    Current data support OGM as a complementary component of genomic workups rather than a replacement for all existing assays. As analytical standards mature and outcome-linked evidence expands, OGM has strong potential to improve genomic risk stratification, refine disease classification and advance precision diagnostics in myeloid neoplasms.
    Review • Journal
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    KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus)
    12d
    The MCU-MECOM Axis Orchestrates Glioblastoma Progression by Remodeling Mitochondrial Dynamics and Quality Control via MAMs. (PubMed, Int J Biol Sci)
    Pharmacological blockade and autophagy-rescue experiments (using si-ATG5 and chloroquine) indicate that this mitophagy-dependent quality control promotes tumor migration and buffers reactive oxygen species (ROS) to sustain OXPHOS capacity...In an independent external validation cohort, MAMs-Net achieved an AUC of 0.95 for glioma pathological stratification. This study characterizes an MCU-MECOM structural-metabolic circuit that supports GBM survival under calcium overload, identifying a potential therapeutic target and providing a pathophysiologically interpretable, AI-driven tool for glioma evaluation.
    Journal
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    MECOM (MDS1 And EVI1 Complex Locus) • ATG5 (Autophagy Related 5) • CD46 (CD46 Molecule)
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    chloroquine phosphate
    19d
    Polyclonal evolution of lymphoproliferative disorders in XLP1. (PubMed, J Hum Immun)
    Gene Ontology analysis showed upregulation of adaptive immune response genes, including various IgH and TCR genes, suggesting polyclonal lymphocyte proliferation. Overall, LPD associated with XLP1 may originate from polyclonal lymphocyte expansion, either in the presence or absence of EBV infection, and subsequently progress to malignancy through somatic variants.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • CARD11 (Caspase Recruitment Domain Family Member 11) • MECOM (MDS1 And EVI1 Complex Locus) • GNA13 (G Protein Subunit Alpha 13) • P2RY8 (P2Y Receptor Family Member 8) • CCND3 (Cyclin D3) • IRF4 (Interferon regulatory factor 4)
    21d
    Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN (clinicaltrials.gov)
    P1, N=102, Active, not recruiting, Jacqueline Garcia, MD | Trial completion date: Mar 2027 --> Mar 2030
    Trial completion date
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • DEK (DEK Proto-Oncogene) • RIT1 (Ras Like Without CAAX 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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    TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • Chr del(5q)
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    Venclexta (venetoclax) • azacitidine • Inqovi (decitabine/cedazuridine) • fludarabine IV • busulfan
    23d
    Comprehensive Molecular Characterization of High-Grade Endometrial Cancer in an Ancestrally-Diverse Cohort. (PubMed, bioRxiv)
    Notably, focal amplification of the EVI1 transcription factor (encoded at the MECOM locus) was significantly more frequent in African ancestry patients and associated with poorer clinical outcomes in an external validation cohort. Additionally transcriptome analysis revealed decreased CD8+ T cell infiltration with increasing African ancestry, suggesting tumor immune microenvironment differences with potential therapeutic implications.
    Journal
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    CD8 (cluster of differentiation 8) • MECOM (MDS1 And EVI1 Complex Locus)
    23d
    Durvalumab plus HAIC-FOLFOX followed by maintenance durvalumab for hepatocellular carcinoma with major portal invasion: phase 2 DurHope study. (PubMed, Nat Commun)
    We conducted a single-arm phase 2 study (DurHope) enrolling 30 patients with Vp3/4 PVTT receiving durvalumab plus hepatic arterial infusion therapy (HAIC) of FOLFOX regimen (fluorouracil, leucovorin, and oxaliplatin) as first-line treatment. These data suggested the promising efficacy and generally tolerable toxicity of Durvalumab plus HAIC-FOLFOX in patients with Vp4 PVTT and provided candidate biomarkers. ClinicalTrials.gov number: NCT04945720.
    P2 data • Journal • PD(L)-1 Biomarker
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    MECOM (MDS1 And EVI1 Complex Locus)
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    Imfinzi (durvalumab) • 5-fluorouracil • oxaliplatin • leucovorin calcium
    1m
    MECOM promotes leukemia progression and inhibits mast cell differentiation through functional competition with GATA2. (PubMed, Leukemia)
    Furthermore, we generated a knockin mouse model harboring a C-terminal ZFD mutation, which successfully recapitulated the clinical phenotypes of MECOM-associated syndromes, including reduction of HSCs and B cells. Collectively, our findings define C-terminal ZFD mutations as loss-of-function mutations with impaired DNA binding, uncover the MECOM-GATA2 axis as a key regulatory pathway, and provide a valuable mouse model for understanding MECOM-associated syndromes.
    Journal
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    MECOM (MDS1 And EVI1 Complex Locus) • GATA2 (GATA Binding Protein 2)
    2ms
    Genome-wide screening identifies ZFP91 as a key regulator of EVI1 in myeloid leukemia. (PubMed, Oncogene)
    Our data showed that the ZFP91-EVI1 axis plays a critical role for activation of EVI1 in myeloid leukemia. Our screening approach represents a powerful and unbiased method for identifying expression regulators that can be broadly applied across a range of contexts.
    Journal
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    MECOM (MDS1 And EVI1 Complex Locus)