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    BIOMARKER:

    DNMT3A mutation + NPM1 mutation

    i
    Other names: DNMT3A, DNA Methyltransferase 3 Alpha, DNA (Cytosine-5-)-Methyltransferase 3 Alpha, DNA (Cytosine-5)-Methyltransferase 3A, DNA MTase HsaIIIA, DNA Cytosine Methyltransferase 3A2, DNA Methyltransferase HsaIIIA, DNMT3A2, Dnmt3a, Nucleophosmin (Nucleolar Phosphoprotein B23, Numatrin), Testicular Tissue Protein Li 128, Nucleolar Protein NO38, Numatrin, NPM1, Nucleophosmin 1, Nucleophosmin/Nucleoplasmin Family, Member 1, Nucleolar Phosphoprotein B23
    Entrez ID:
    4869; 1788
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    20d
    Quizartinib with donor lymphocyte infusion for post-transplant relapse of FLT3-ITD-positive acute myeloid leukemia. (PubMed, Int J Hematol)
    The patient achieved hematological CR on day 163 and remained in molecular CR 3 years after allo-HCT without adverse effects. Quizartinib combined with DLI may be a feasible treatment for early relapse of FLT3-ITD-positive AML after allo-HCT, even with concurrent DNMT3A and NPM1 mutations.
    Journal • Post-transplantation
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation • DNMT3A R882
    |
    Vanflyta (quizartinib)
    1year
    Overexpression of the Signaling Integrator Gab2 Accelerates AML Development in Mice with Dnmt3aR878H and Npm1cA Mutations (ASH 2023)
    These data nominate GAB2 overexpression as a factor that may be relevant for the progression of founding clones with DNMT3A and NPM1 mutations to overt AML. Additional studies to define its protein interactome in preleukemic cells, its mechanism of action, and how leukemia-causing mutations in DNMT3A and NPM1 shape the fitness landscape to select for GAB2 overexpression are underway.
    Preclinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CD34 (CD34 molecule)
    |
    NPM1 mutation • KIT mutation • DNMT3A mutation • PTPN11 mutation • CBL mutation • DNMT3A mutation + NPM1 mutation • FLT3 expression • PAK1 overexpression
    over1year
    RETAINED FUNCTIONAL NORMAL AND/OR PRE-LEUKEMIC HSCS IN THE BONE MARROW ARE ASSOCIATED TO GOOD PROGNOSIS IN DNMT3A MUT NPM1 MUT AML PATIENTS (EHA 2023)
    These data suggest that the presence of normal and/or preleukemic HSCs with multilineage engrafting potential in the bone marrow of naïve patients is associated with good response to standard chemotherapy, providing a basis for the development of novel predictive biomarkers for standard chemotherapy regime. DNMT3A, AML, Leukemic stem cell, Stem cell marker
    Clinical • IO biomarker
    |
    NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CD38 (CD38 Molecule) • CD34 (CD34 molecule) • ADGRG1 (Adhesion G Protein-Coupled Receptor G1)
    |
    NPM1 mutation • DNMT3A mutation • CD34 positive • DNMT3A mutation + NPM1 mutation
    2years
    Single Cell Genotypic and Phenotypic Analysis of Measurable Residual Disease in Acute Myeloid Leukemia (ASH 2022)
    Larger studies are needed to comprehensively elucidate the clonal architecture of MRD and study the dynamics of clonal evolution by comparing clonal architecture and immunophenotype at diagnosis and relapse. Our study paves the road for identifying/eradicating high-risk MRD clones and preventing relapse through a better understanding of the molecular drivers of MRD.
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • CD34 (CD34 molecule)
    |
    TP53 mutation • NRAS mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • RUNX1 mutation • SRSF2 mutation • DNMT3A mutation + NPM1 mutation
    2years
    Identification of the Thyrotropin-Releasing Hormone (TRH) as a Novel Biomarker in the Prognosis for Acute Myeloid Leukemia. (PubMed, Biomolecules)
    Furthermore, we demonstrated that the expression of TRH in AML could be used to improve the ELN 2017 risk stratification system. In conclusion, our preliminary analysis revealed that TRH, a novel biomarker for AML patients, could be used to evaluate the survival of AML.
    Journal
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)
    |
    NPM1 mutation • KIT mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation
    over2years
    TRANSCRIPTIONAL AND TRANSLATIONAL SIGNATURES OF TRIPLE MUTATED DNMT3AKO/FLT3ITD/NPM1C MICE SHOW ALTERED RNAS PROCESSING AND CELL CYCLE PROGRESSION (EHA 2022)
    Conclusion The leukemic DNMT3A KO / FLT3 ITD / NPM1 c genotype is characterized by unique transcriptional and translational signatures. The information about deregulated pathways and altered protein synthesis establishes the rational basis for designing new therapeutic approaches in this poor prognosis AML genotype.
    Preclinical
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • HOXA9 (Homeobox A9) • RAC1 (Rac Family Small GTPase 1)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation • FLT3-ITD expression
    over2years
    PRECLINICAL AND CLINICAL SIGNS OF RVU120 EFFICACY, A SPECIFIC CDK8/19 INHIBITOR IN DNMT3A MUTATION POSITIVE AML AND HR-MDS (EHA 2022)
    Preliminary evidence of clinical response to RVU120 has been also shown in R/R AML and HR-MDS patients positive for DNMT3A mutations. Further molecular studies in greater number of patients under RVU120 treatment are ongoing and will provide evidence for predictive markers of response to RVU120 in AML.
    Preclinical
    |
    NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CDK9 (Cyclin Dependent Kinase 9)
    |
    NPM1 mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation
    |
    RVU120