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    GENE:

    KMT2A (Lysine Methyltransferase 2A)

    i
    Other names: KMT2A, Lysine Methyltransferase 2A, Histone-Lysine N-Methyltransferase 2A, CXXC7, TRX1, Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog, Drosophila), Lysine (K)-Specific Methyltransferase 2A, CXXC-Type Zinc Finger Protein 7, Lysine N-Methyltransferase 2A, Zinc Finger Protein HRX, Trithorax-Like Protein, HTRX1, MLL1A, MLL1, MLL, Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax (Drosophila) Homolog), Myeloid/Lymphoid Or Mixed-Lineage Leukemia Protein 1, Myeloid/Lymphoid Or Mixed-Lineage Leukemia, Mixed Lineage Leukemia 1, WDSTS, ALL1, HTRX
    13h
    Tafasitamab (MOR00208) in Pediatric Patients With Relapsed or Refractory Acute B Lineage Leukemia (clinicaltrials.gov)
    P1/2, N=20, Recruiting, University Hospital Tuebingen | Trial completion date: Mar 2027 --> Feb 2029 | Trial primary completion date: Mar 2027 --> Jul 2028
    Trial completion date • Trial primary completion date
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    TP53 (Tumor protein P53) • KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)
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    TP53 mutation • CD19 positive
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    Monjuvi (tafasitamab-cxix)
    3d
    Identification of cellular hierarchy in paediatric acute myeloid leukaemia: The Japan Children's Cancer Group trial (JCCG AML-12). (PubMed, Br J Haematol)
    LSPC-Cycle, FLT3-ITD and NUP98::KDM5A were considered independent prognostic factors in multivariate analysis. Findings indicate the prognostic relevance of cellular hierarchy and the importance of integrating hierarchy-specific molecular profiles for improved risk stratification and treatment formulation.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NUP214 (Nucleoporin 214) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GATA1 (GATA Binding Protein 1) • GLIS2 (GLIS Family Zinc Finger 2) • KDM5A (Lysine Demethylase 5A) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
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    FLT3-ITD mutation
    4d
    Mesothelin Expression in Acute Leukemia: Correlations With Immunophenotype, Cytogenetics, and Mutational Status. (PubMed, Appl Immunohistochem Mol Morphol)
    In AML, it correlated with CD33 expression and inv(16)/t(16;16). In conclusion, mesothelin is rare in ALL but enriched in specific AML subtypes and not prognostic for survival.
    Journal • IO biomarker
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    NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • KMT2A (Lysine Methyltransferase 2A) • MSLN (Mesothelin) • CD38 (CD38 Molecule) • KDM6A (Lysine Demethylase 6A) • CD33 (CD33 Molecule) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6) • ITGAX (Integrin Subunit Alpha X) • CBLC (Cbl Proto-Oncogene C)
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    NPM1 mutation • CBL mutation
    4d
    Optical genome mapping detects cryptic high-risk and targetable abnormalities in adult AML. (PubMed, Br J Haematol)
    Survival analyses suggested a trend towards poorer outcomes in patients reclassified as adverse, though the small sample limits definitive conclusions. In low-complexity AML, OGM provides substantial incremental diagnostic value, detecting cryptic high-risk and targetable abnormalities, supporting its use as a complementary tool.
    Journal
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    KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)
    6d
    A phase II clinical trial of epalolitoporvorellimab (QL1706) in combination with fruquintinib for the treatment of immunocompetent pMMR/MSS metastatic colorectal cancer that has failed second- or higher lines of therapy. (ChiCTR2500112464)
    P2, N=18, Not yet recruiting, Harbin Medical University Affiliated Cancer Hospital; Harbin Medical University Affiliated Cancer Hospital
    New P2 trial
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    PD-L1 (Programmed death ligand 1) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • KMT2A (Lysine Methyltransferase 2A) • POLD1 (DNA Polymerase Delta 1)
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    ARID1A mutation
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    Fruzaqla (fruquintinib) • Qibeian (iparomlimab/tuvonralimab)
    7d
    mTOR Modulation Affects Galectin-1 Expression in KMT2A-rearranged Acute Lymphoblastic Leukemia Cells. (PubMed, Anticancer Res)
    Targeting mTOR signaling contributes to the regulation of Galectin-1 immune checkpoint activity in KMT2Ar-ALL. Inhibition of mTOR may represent a potential therapeutic strategy to overcome immune evasion in this leukemia subtype.
    Journal • IO biomarker
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    mTOR (Mechanistic target of rapamycin kinase) • KMT2A (Lysine Methyltransferase 2A) • LGALS1 (Galectin 1)
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    everolimus
    7d
    Research Progress on the KMT2A-AFF3 Fusion Gene in Childhood Acute Lymphoblastic Leukemia: Mechanisms, Clinical Implications, and Therapeutic Strategies. (PubMed, Curr Issues Mol Biol)
    This review highlights the evidence defining its poor prognosis, which is primarily driven by profound chemoresistance to conventional therapies, including glucocorticoids. Finally, we discuss the rapidly evolving therapeutic landscape, detailing the limitations of standard intensive chemotherapy and the immense promise of novel targeted strategies, such as Menin inhibitors (e.g., Revumenib), DOT1L inhibitors, and immunotherapies (e.g., CAR-T cells, Blinatumomab), which hold the potential to revolutionize outcomes for this high-risk leukemia subtype.
    Review • Journal
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    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • MEIS1 (Meis Homeobox 1) • MME (Membrane Metalloendopeptidase) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • AFF3 (AF4/FMR2 Family Member 3)
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    Blincyto (blinatumomab) • Revuforj (revumenib)
    8d
    Analysis of factors influencing the prognosis of pediatric acute myeloid leukemia based on minimal residual disease with different detection methods (PubMed, Zhonghua Yi Xue Za Zhi)
    The 3-year overall survival rates and event-free survival (EFS) rates were 80.7% and 69.4%, respectively. Multivariate Cox regression analysis revealed that gene MLL rearrangement (excluding MLL-AF9) (HR=3.071, 95%CI: 1.024-9.205) and positive molecular MRD after Induction Course Ⅱ therapy (HR=5.571, 95%CI: 1.244-24.957) were risk factors for EFS in pediatric AML patients.
    Retrospective data • Journal • Minimal residual disease
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    KMT2A (Lysine Methyltransferase 2A)
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    MLL rearrangement
    8d
    MOMENTUM: Study of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression (clinicaltrials.gov)
    P1/2, N=84, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting
    Enrollment open • First-in-human
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    KMT2A (Lysine Methyltransferase 2A)
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    Noxafil (posaconazole)
    9d
    Menin Inhibition in Acute Myeloid Leukemia: Pathobiology, Progress and Promise. (PubMed, Biomedicines)
    We evaluate the latest data on various menin inhibitors-both as monotherapy and in combinations-emphasizing their efficacy and safety profiles. As new evidence continues to accumulate with recent drug approvals and ongoing randomized, phase 3 studies, menin inhibitors are rapidly becoming a component of the AML treatment paradigm for relapsed/refractory and likely newly diagnosed disease.
    Review • Journal
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    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • HOXA9 (Homeobox A9) • MEIS1 (Meis Homeobox 1)
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    NPM1 mutation • MLL rearrangement