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BIOMARKER:

KMT2A rearrangement + RAS mutation

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, RAS, Rat Sarcoma Virus
Entrez ID:
6ms
Cladribine Combined with Homoharringtonine and Cytarabine Achieves a High Remission Rate in Adult Patients with De Novo Acute Myeloid Leukemia, Especially for Adverse-Risk Group: A Prospective, Single Center, Single-Arm, Phase 2 Study (ASH 2023)
We propose the CHA regimen as a novel, effective, and safe chemotherapy regimen for newly diagnosed adult AML patients with remarkable potency in treating adverse-risk group patients, especially those with KMT2A rearrangements and RAS mutations that are otherwise resistant to BCL-2 inhibitor-based therapies, but a limited effect on FLT3 mutated AML patients.
Clinical • P2 data • IO biomarker
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TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • MCL1 (Myeloid cell leukemia 1) • KMT2A (Lysine Methyltransferase 2A)
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TP53 mutation • FLT3 mutation • RAS mutation • KMT2A rearrangement • MLL rearrangement • MLL mutation • KMT2A rearrangement + RAS mutation
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cytarabine • cladribine • Synribo (omacetaxine mepesuccinate)
12ms
COMBINING MENIN AND MEK INHIBITION TO TREAT CHILDREN WITH POOR PROGNOSTIC KMT2A-R RAS-MUTANT ACUTE LEUKEMIA (EHA 2023)
We evaluated the combination of RAS/MAPK pathway inhibition by the MEK1/2 inhibitor selumetinib with the Menin inhibitor VTP-50469 (SNDX-5613) in a genetically defined, poor prognostic subgroup of pediatric leukemia harboring KMT2A-r with RAS mutations. The findings in our preclinical study suggest a promising, readily translatable treatment for patients with KMT2A-racute leukemias harboring RAS mutations. Mechanistically, enhanced downregulation of both MYC signaling and the RAS/MAPK pathway with the combinatorial therapy is likely a strong contributor to the observed efficacy. MYC, Acute leukemia, KMT2A
Clinical
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KMT2A (Lysine Methyltransferase 2A) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • MEIS1 (Meis Homeobox 1)
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RAS mutation • KMT2A mutation • KMT2A rearrangement + RAS mutation
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Koselugo (selumetinib) • revumenib (SNDX-5613) • VTP-50469