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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
    15d
    Highly effective combination of BRG1/BRM inhibitor with BET inhibitor or decitabine for high-risk MECOM-rearranged AML. (PubMed, Hemasphere)
    In AML with 3q26.2 rearrangements (r) the distal GATA2 hematopoietic enhancer becomes aberrantly relocated leading to activation of EVI1 expression. In patient-derived xenograft (PDX) models of AML with MECOM-r, compared to each drug alone, co-treatment with FHD-286 and BETi OTX015 significantly reduced AML burden and improved survival, without inducing significant toxicity. These findings highlight the FHD-286-based combinations as promising therapy of AML with chromosome 3q26.2 rearrangement and EVI1 overexpression.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • MECOM (MDS1 And EVI1 Complex Locus) • GATA2 (GATA Binding Protein 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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    decitabine • birabresib (OTX015) • camibirstat (FHD-286)
    21d
    MECOM Function is Critical for AR-Driven Treatment-Resistant Prostate Cancer. (PubMed, Cancer Res)
    In prostate cancer, MECOM was exclusively overexpressed in both CRPC and enzalutamide-resistant CRPC and interacted with AR in the nucleus...These insights reveal the crucial role of EVI1 in regulating cell survival within the context of an AR-reprogrammed chromatin landscape. More importantly, the findings suggest that MECOM overexpression may be another biomarker that could significantly broaden the use of PARP inhibitors beyond those with HRR gene mutations.
    Journal • PARP Biomarker
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    HRD (Homologous Recombination Deficiency) • MECOM (MDS1 And EVI1 Complex Locus)
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    Xtandi (enzalutamide)
    27d
    Optical genome mapping as a high-resolution tool for uncovering cytogenetic complex and cryptic alterations in a cohort of patients with MDS and AML. (PubMed, NPJ Precis Oncol)
    The identified abnormalities have shown significant and potential clinical implications. Additionally, the discovery of novel alterations could offer insights into previously unknown pathogenic mechanisms, enhancing our understanding of AML and MDS pathogenesis.
    Journal
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    KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus)
    1m
    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: Feb 2026 --> Mar 2027 | Trial primary completion date: Dec 2025 --> May 2026
    Trial completion date • Trial primary 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
    1m
    Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • 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) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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    TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation • Chr del(5q)
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    cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)
    1m
    Off-the-shelf NK Cells + SCT for Myeloid Malignancies (clinicaltrials.gov)
    P2, N=24, Completed, M.D. Anderson Cancer Center | Phase classification: P1/2 --> P2
    Phase classification
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • DEK (DEK Proto-Oncogene)
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    TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • Chr del(5q)
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    cyclophosphamide • melphalan • fludarabine IV • mesna • Neupogen (filgrastim)
    2ms
    BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML. (PubMed, Leukemia)
    In a MECOM-r AML PDX model, mivebresib with dactolisib or LCL161, was superior to monotherapy or vehicle in reducing AML burden and increasing mouse survival. These findings highlight that cotreatment with BETi and PI3K/mTOR or IAP inhibitor exerts superior in vitro and in vivo efficacy in MECOM-r AML cells and support further evaluation of these BETi-based combinations.
    Journal
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2L1 (BCL2-like 1) • MECOM (MDS1 And EVI1 Complex Locus) • GATA2 (GATA Binding Protein 2) • BRD4 (Bromodomain Containing 4) • XIAP (X-Linked Inhibitor Of Apoptosis)
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    dactolisib (RTB101) • mivebresib (ABBV 075) • LCL161
    2ms
    Thrombopoietin increases susceptibility for EVI1 + KMT2A-MLLT3-driven AML expressing stem cell genes linked to poor outcome. (PubMed, Nat Commun)
    Knockdown experiments show exclusive MECOM-dependency of human EVI1high KMT2A-rearranged OCI-AML4 cells while reduction of IL12Rβ2 also impairs clonogenic growth of EVI1low MOLM-13, THP-1 or HL-60 AML cells. Collectively, we show that exogenous factors like TPO can increase the susceptibility for iKMT2A-MLLT3-driven HSC-originating Evi1+ AML expressing stem cell genes linked to transformation maintenance of cell lines, and poor disease outcome of patients.
    Journal
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    KMT2A (Lysine Methyltransferase 2A) • MECOM (MDS1 And EVI1 Complex Locus) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
    2ms
    Molecular Characterization of MECOM Rearrangements in Two Cases with Myelodysplastic Syndrome and t(2;3)(p23;q26.2). (PubMed, Cytogenet Genome Res)
    She was treated with azacitidine...Conclusion Our findings highlighted that, despite cytogenetic similarity, different t(2;3) translocations may exert distinct regulatory effects depending on the precise breakpoint locations. Thus, molecular characterization of MECOM rearrangements is critical for understanding disease pathogenesis and prognosis in myeloid neoplasms and may lead to the development of novel treatment.
    Journal
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    MECOM (MDS1 And EVI1 Complex Locus) • ZFP36 (ZFP36 Ring Finger Protein)
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    azacitidine
    2ms
    MECOM amplified endometrial cancer, a novel subset of copy number high tumors associated with poor prognosis. (PubMed, Gynecol Oncol Rep)
    ECs with MECOM amplification are associated with poor clinical outcomes, even in the absence of CCNE1 or ERBB2 amplification. The current literature is limited, and further studies are warranted to determine the role of MECOM amplification in ECs.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • MECOM (MDS1 And EVI1 Complex Locus)
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    TP53 mutation • HER-2 amplification
    2ms
    Prognostic value assessment and in vitro validation of mitochondria-ferroptosis-related genes in multiple myeloma. (PubMed, Sci Rep)
    RT-qPCR results showed that NLRP7 and PRDM13 were significantly upregulated in MM group, while GPR15 and CRIM1 were significantly downregulated in MM group (p < 0.05). In this study, 5 MFRGs were identified as prognostic genes (GPR15, NLRP7, ZNF208, PRDM13, and CRIM1) for MM, which provide reference significance for the prognosis of MM.
    Preclinical • Journal
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    MECOM (MDS1 And EVI1 Complex Locus)