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    BIOMARKER:

    MECOM rearrangement

    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
    Entrez ID:
    2122
    Related biomarkers:
    Mutation
    Others
    6ms
    GENE FUSIONS ARE A PUTATIVE MECHANISM THAT DIMINISHES SENSITIVITY TO VENETOCLAX-HYPOMETHYLATING AGENTS COMBINATION IN ACUTE MYELOID LEUKEMIA (SIE 2023)
    Appealing patterns of resistance emerged from genomic analysis: the “activating like� signature may help define a specific target among tyrosine kinase inhibitors, while “self-renewal like� patients may benefit from histone deacetylase inhibitors (as we previously published). HOXA genes overexpression open a novel therapeutic options for selected patients.
    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • BAX (BCL2-associated X protein) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • CCND2 (Cyclin D2) • DDX5 (DEAD-Box Helicase 5) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B) • PER1 (Period Circadian Clock 1) • TBL1XR1 (TBL1X Receptor 1)
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    NRAS mutation • CBL mutation • MECOM rearrangement • PDGFRB mutation
    |
    TruSight RNA Pan-Cancer Panel
    |
    Venclexta (venetoclax)
    6ms
    Clinical Characteristics and Outcomes of Myeloid Neoplasms with Mecom Rearrangement: Results from a Nationwide Multicenter Study (ASH 2023)
    Among 3 MDS with MECOM rearrangement, one patient received azacitidine with investigational drug (sabatolimab/placebo) and achieved complete hematologic response. Chemotherapy should be avoided in this subtype due to non-responsiveness, hypomethylating agent showed benefit and can be considered as a bridging treatment before stem cell transplantation. Novel therapy targeting MECOM gene should be further explored to improve outcomes in this AML subtype.
    Clinical
    |
    MECOM (MDS1 And EVI1 Complex Locus)
    |
    MECOM rearrangement
    |
    azacitidine • sabatolimab (MBG453)
    6ms
    CPX-351 with Venetoclax in Patients with Relapsed/Refractory Acute Myeloid Leukemia: Results of a Phase Ib Study (ASH 2023)
    In this phase Ib dose escalation study, standard dose CPX-351 combined with 7 days of Ven was found to safe and tolerable in pts with rAML. The combination produced encouraging response rates in a poor risk population, including those with prior Ven treatment, allowing a significant proportion to undergo allo-SCT and extended survival. The RP2D is being studied in pts with newly diagnosed and less heavily pretreated AML.
    Clinical • P1 data • IO biomarker
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    TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • MECOM (MDS1 And EVI1 Complex Locus)
    |
    TP53 mutation • DNMT3A mutation • MECOM rearrangement
    |
    Venclexta (venetoclax) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
    6ms
    Novel Mechanisms of Venetoclax Resistance in Acute Myeloid Leukemia Based on Genomic Rearrangements (ASH 2023)
    Through deep transcriptomic characterization combined with conventional diagnostics, this analysis uncovered novel mechanisms of VEN resistance while confirming established ones. The distinct gene expression patterns may help tailor targeted therapies, with patients showing the "activating-like" signature potentially benefiting from tyrosine kinase inhibitors and those with the "self-renewal like" signature possibly responding well to histone deacetylase inhibitors. Furthermore, HOXA gene overexpression presents an exciting therapeutic opportunity for selected patients.
    IO biomarker
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR (Fibroblast Growth Factor Receptor) • JAK2 (Janus kinase 2) • MCL1 (Myeloid cell leukemia 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • BAX (BCL2-associated X protein) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • CCND2 (Cyclin D2) • DDX5 (DEAD-Box Helicase 5) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B) • PER1 (Period Circadian Clock 1) • GSDMC (Gasdermin C) • TBL1XR1 (TBL1X Receptor 1)
    |
    NRAS mutation • CBL mutation • MCL1 expression • NRAS G13 • MECOM rearrangement • PDGFRB mutation
    |
    TruSight RNA Pan-Cancer Panel
    |
    Venclexta (venetoclax)
    6ms
    Whole Genome and Transcriptome Sequencing of 21 Paired Chronic and Blast Phase CML Cases: Acquisition of Genomic Alterations, Changes in the Transcriptomic Profiles and Occurrence of B-Cell Receptor Rearrangements (ASH 2023)
    1) Extensive genetic profiling indicated a substantial clonal evolution in the progression from CP to BP CML including loss of ASXL1 mutations, expansion of RUNX1 mutated clones, multiple CNA, and the frequent acquisition of a BCR rearrangement in BP with a transcriptomic phenotype resembling B-ALL. 2) A subset of CML cases in CP already showed a transcriptomic phenotype resembling acute leukemia indicating a rapid progression to BP. 3) The presence of a RUNX1 mutated subclone or a clonal BCR rearrangement seem to represent a warning signal in CML CP.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MECOM (MDS1 And EVI1 Complex Locus) • MGA (MAX Dimerization Protein MGA) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
    |
    DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • CDKN2A deletion • TET2 mutation • MLL rearrangement • BCOR mutation • IKZF1 deletion • WT1 mutation • MECOM rearrangement • SETD2 mutation • ABL1 fusion • MGA mutation • MLL3 mutation
    6ms
    Stem-Cell Enriched Cellular Hierarchy of TP53 Mutant Acute Myeloid Leukemia Is Vulnerable to Targeted Protein Degradation of c-MYC (ASH 2023)
    GT19715 but did not reduce total mouse BM CD45+ cells, suggesting favorable toxicity profiles of GT19715. In conclusion, TP53mut AML comprised highly enriched LSC populations compared to TP53wt AML and targeting of c-MYC protein is highly effective in TP53mut AML in vitro and in vivo with a therapeutic window between AML LSC and normal hematopoietic cells.
    IO biomarker
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CRBN (Cereblon) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • MECOM (MDS1 And EVI1 Complex Locus)
    |
    TP53 mutation • NRAS mutation • TP53 wild-type • MYC expression • MECOM rearrangement • TP53 Y220C
    6ms
    Pre-Existing Myeloid Subclones May Account for a Subset of Acute Myeloid Leukemias and Myelodysplastic Neoplasms in Patients with Pre-Existing or Contemporary Lymphoid Disorders (ASH 2023)
    Interestingly, 7 patients (64%) were diagnosed while they were receiving lenalidomide after a median exposure to lenalidomide of 8.8 months (4.9 – 30.73)... The incidence of AML or MDS associated with lymphoid disease is low. Furthermore, the population is remarkably heterogeneous. The characteristics and the timing of onset of the disease account for different ontogenesis; a portion of the patient has a disease that harbors complex alterations, while the most frequent origin of AML and MDS can be researched in pre-existing or contemporary hematopoietic clones, that overall account for a whole bone-marrow disease.
    Clinical
    |
    TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • MECOM (MDS1 And EVI1 Complex Locus)
    |
    TP53 mutation • MECOM rearrangement
    |
    lenalidomide
    7ms
    Prolonged cytopenia after anti-BCMA-CAR-T-Cell therapy in myeloma: Donor cell derived acute myeloid leukemia (DCL) in a patient after allogeneic hematopoietic cell transplantation (DGHO 2023)
    Venetoclax was initiated and a second allo-HSCT was planned. This is, to the best of our knowledge, the first reported case of DCL as cause of prolonged cytopenia in a patient after CAR-T-Cell therapy. Cytopenia after CAR-T-Cell therapy is common and mostly attributed to lymphodepletion, bridging-therapy or severe CRS. Prolonged/recurrent cytopenia is reported in a various rate (up to 40% at d+90 in Ide-Cel RWD) and different mechanisms have been discussed.
    Clinical • CAR T-Cell Therapy
    |
    MECOM (MDS1 And EVI1 Complex Locus)
    |
    Chr del(17p) • MYC rearrangement • MECOM rearrangement
    |
    Venclexta (venetoclax) • Abecma (idecabtagene vicleucel)
    8ms
    BCR::ABL1-Positive (Ph+) T-Lymphoblastic Leukemia/Lymphoma With Concurrent Chronic Myeloid Leukemia: Report of 2 Cases With Additional MECOM Rearrangement in 1 Case (CAP 2023)
    The patient in case 1 received standard chemotherapy for T-ALL/LBL, plus dasatinib, with pretransplantation biopsy showing BCR::ABL1 fusion transcript at 1.71% international scale and rare cells, by cytogenetics, showing BCR::ABL1 and ETV6 rearrangements (negative MECOM rearrangement). To our knowledge, case 1 is the first reported adult case with a MECOM rearrangement in concurrently diagnosed T-ALL/LBL and CML (previously reported in the pediatric setting). The above rare cases of T-ALL/LBL and concurrent CML highlight the importance of a comprehensive clinical and laboratory evaluation to fully elucidate a patient’s disease status in the context of CML.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1) • ETV6 (ETS Variant Transcription Factor 6) • MECOM (MDS1 And EVI1 Complex Locus)
    |
    MECOM rearrangement • ABL1 fusion
    |
    dasatinib
    9ms
    Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center (PubMed, Zhonghua Xue Ye Xue Za Zhi)
    There was no significant difference in the frequency of other gene mutations between the two groups. According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • MECOM (MDS1 And EVI1 Complex Locus) • SETBP1 (SET Binding Protein 1)
    |
    NPM1 mutation • ASXL1 mutation • TET2 mutation • KMT2A rearrangement • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • MLL mutation • MECOM rearrangement