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    BIOMARKER:

    KMT2A-PTD

    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
    Entrez ID:
    4297
    Related biomarkers:
    Expression
    Mutation
    Fusion
    Others
    11ms
    A multicenter, open phase I/ II clinical study to evaluate the safety, pharmacokinetics and efficacy of menin inhibitor BN104 in the treatment of patients with acute myeloid leukemia (ChiCTR2400093165)
    P1/2, N=135, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University
    New P1/2 trial
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • AFF1 (AF4/FMR2 Family Member 1) • MEIS1 (Meis Homeobox 1) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement • KMT2A-PTD • MEIS1 overexpression • NUP98 rearrangement
    |
    cytarabine • azacitidine
    1year
    Pre-transplantation levels of lysine (K)-specific methyltransferase 2A (KMT2A) partial tandem duplications can predict relapse of acute myeloid leukemia patients following haploidentical donor hematopoietic stem cell transplantation. (PubMed, Blood Sci)
    In multivariable analysis, KMT2A-PTD ≥1% before HID HSCT was the only independent risk factor for relapse (hazard ratio [HR]: 4.90; 95% CI: 1.22-19.59; P = .025). Thus, pre-transplantation levels of KMT2A-PTD could predict relapse in AML patients following HID HSCT.
    Journal • Pre-transplantation
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    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A-PTD
    over1year
    THE CLINICAL IMPACT OF CONCURRENT GENE MUTATIONS AND CYTOGENETIC ABNORMALITIES ON NPM1-MUTATED AML: A RETROSPECTIVE COHORT STUDY OF 1,520 PATIENTS (EHA 2024)
    NPM1 mutations were identified in 21. 7% of 1,520 patients. Patients with NPM1mut were older and had higherWBC counts and LDH levels, and more often had a normal karyotype, but less adverse cytogenetic features,including monosomal karyotype and MR cytogenetic abnormalities at diagnosis compared to NPM1wtpatients.
    Retrospective data
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    TP53 mutation • FLT3-ITD mutation • IDH1 mutation • FLT3 mutation • NPM1 mutation • DNMT3A mutation • TET2 mutation • KMT2A-PTD
    |
    TruSight Myeloid Sequencing Panel
    over1year
    Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia. (PubMed, Cancers (Basel))
    KMT2A-PTDs are complex gene rearrangements that cannot be fully ascertained using a single genomic platform. MLPA, NGS panels, and OGM are complementary technologies applied in standard-of-care testing for AML patients. MLPA and NGS panels are designed for targeted copy number analysis; however, our results showed that integration of concurrent genomic alterations is needed for accurate KMT2A-PTD identification. Unbalanced chromosomal rearrangements overlapping with KMT2A can interfere with the diagnostic sensitivity and specificity of copy-number-based KMT2A-PTD detection methodologies.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • KMT2A-PTD
    almost2years
    Detection of KMT2A-PTDs and KMT2A fusions using next generation sequencing (AACR 2024)
    We characterize the KMT2A fusions present in myeloid malignant samples. We also describe the abundance of KMT2A PTDs in both healthy donor and myeloid samples, with myeloid cases showing significantly higher PTD read counts. KMT2A PTD read count >2000 is present only in malignant samples but not in healthy donors.
    Next-generation sequencing
    |
    KMT2A (Lysine Methyltransferase 2A) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
    |
    MLL rearrangement • MLL rearrangement • KMT2A-PTD • MLL fusion
    |
    Oncomine Myeloid Assay GX
    2years
    Detection of KMT2A Partial Tandem Duplications ( KMT2A-PTDs) in Healthy Donors Using Next Generation Sequencing (ASH 2023)
    "Not for use in diagnostic procedures. )"
    Clinical
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A-PTD • MLL fusion • MLL-PTD
    |
    Oncomine Myeloid Assay GX
    2years
    Genomic Analyses Unveil the Pathogenesis and Inform on Therapeutic Targeting in KMT2A-PTD AML (ASH 2023)
    Given the results obtained with menin inhibitors in KMT2A-rearranged and NPM1-mutated AML, our findings open an opportunity for exploiting a therapeutic vulnerability in all HOX-AML including KMT2A-PTD AML or AML with high MEN1 expression. Since HOX-AML highly express genes according to the HOX differentiation profile, stage-specific surface proteins coded by these genes would be promising targets.
    Genomic analysis
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • 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) • CD276 (CD276 Molecule) • SRSF2 (Serine and arginine rich splicing factor 2) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PML (Promyelocytic Leukemia) • CD34 (CD34 molecule) • STAG2 (Stromal Antigen 2) • CD14 (CD14 Molecule) • LILRB4 (Leukocyte Immunoglobulin Like Receptor B4) • MEN1 (Menin 1) • CD1D (CD1d Molecule) • CD86 (CD86 Molecule) • HOXB2 (Homeobox B2) • NKX2-3 (NK2 Homeobox 3)
    |
    NPM1 mutation • TET2 mutation • KMT2A rearrangement • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • MLL mutation • MLL translocation • KMT2A expression • KMT2A-PTD • CD1D expression
    2years
    Covalent Menin Inhibitor Bmf-219 in Patients with Relapsed or Refractory (R/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the Covalent-101 Study (ASH 2023)
    Patient B: 70/F, NPM1m, ECOG=1, 125 mg QD, Arm B, 1 prior line of treatment with decitabine and an investigational agent. BMF-219 is generally well tolerated with no DLT observed (and able to be taken with and without CYP3A4 inhibitors) with no pts discontinuing therapy due to toxicity. BMF-219 dose escalation is ongoing and approaching target exposure. BMF-219 demonstrates early signs of clinical activity in different genomic subgroups.
    Clinical • P1 data
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • SETBP1 (SET Binding Protein 1) • NUP214 (Nucleoporin 214)
    |
    MLL mutation • KMT2A-PTD • MLL-PTD
    |
    decitabine • icovamenib (BMF-219)
    2years
    Rapid Clinical Mutation Screening for AML Using the Genexus Platform (ASH 2023)
    The NMAv2 has high specificity, sensitivity, accuracy and reproducibility (inter-lab and intra-lab) with sequencing results generated within 48 hours of assay initiation. As such, the assay is well suited for use to rapidly categorize the genomic alteration of AML to support clinical care in patients with active myeloid malignancies, including those patients potentially enrolled in the myeloMATCH program. Table 1: Results of validation experiment results for the NMAv2 Figure 1: Harmonization results for the NMAv2 between MoCha and MO labs, Right Panel = Indel; Left panel = SNV
    Clinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A-PTD
    |
    Oncomine Myeloid Assay GX
    2years
    Impact of KMT2A-PTD Mutational Subgroups on Outcome of AML Patients after Induction Therapy and Allogeneic Hematopoietic Cell Transplantation (ASH 2023)
    Therefore, some KMT2A-PTD variants could be potentially implemented in AML risk stratification. However, prospective studies and larger patient numbers are needed.
    Clinical
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A mutation • MLL mutation • KMT2A-PTD
    2years
    Gene Expression Machine Learning Models Classify Pediatric AML Subtypes with High Performance (ASH 2023)
    Synthetic upsampling (SMOTE) for the training dataset (n=1369) counteracts bias towards the majority classes and increases performance for the random forest (sensitivity=0.9327; precision=0.9327; specificity=0.9965; F1=0.93; accuracy=0.9933), XGboost (sensitivity=0.9404; precision=0.9404; specificity=0.9969; F1=0.94; accuracy=0.9940) and linear SVM (sensitivity=0.9615; precision=0.9615; specificity=0.9980; F1=0.96; accuracy=0.9962) models. Conjointly, these models demonstrate the utility and effectiveness of a machine learning approach for classifying pAML samples from transcriptome sequencing data, which may have broad clinical and research utility, especially for fusion negative subtypes.
    Clinical • Machine learning
    |
    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) • NUP214 (Nucleoporin 214) • GATA1 (GATA Binding Protein 1) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B)
    |
    KMT2A-PTD