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    BIOMARKER:

    FLT3‐ITD + DNMT3A mutation

    i
    Other names: FLT3, Fms Related Tyrosine Kinase 3, Receptor-Type Tyrosine-Protein Kinase FLT3, Stem Cell Tyrosine Kinase 1, Fms-Like Tyrosine Kinase 3, CD135, FLK-2, STK1, Growth Factor Receptor Tyrosine Kinase Type III, Fetal Liver Kinase 2, 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
    Entrez ID:
    2322; 1788
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    1m
    Sweet syndrome induced by FLT3 inhibitors: case report and literature review. (PubMed, Hematology)
    The FLT3 inhibitor gilteritinib was administered for reinduction therapy after failure of chemotherapy with a combination of venetoclax, decitabine, aclarubicin, cytarabine and granulocyte colony-stimulating factor. Similar cases of Sweet syndrome following FLT3 inhibitor therapy for acute myeloid leukemia were reviewed. Attention should be given to this rare complication when FLT3 inhibitors are used for acute myeloid leukemia therapy, and appropriate treatments need to be administered in a timely manner.
    Review • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • FLT3 mutation • DNMT3A mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation
    |
    Venclexta (venetoclax) • cytarabine • Xospata (gilteritinib) • decitabine • aclarubicin
    5ms
    Distinct karyotypic and mutational landscape in trisomy AML. (PubMed, Br J Haematol)
    NRAS mutations were associated with poor outcome in trisomy AML, whereas DNMT3A and FLT3-ITD mutations had neutral effect. Trisomy AML appeared biologically distinct from CN-AML.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • BCOR (BCL6 Corepressor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SMC1A (Structural Maintenance Of Chromosomes 1A)
    |
    KRAS mutation • NRAS mutation • FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation • CEBPA mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation
    6ms
    RUNX1 Mutation Does Not Significantly Impact the Outcome of Newly Diagnosed adult AML: A Retrospective Study of Chinese AML Patients (ASH 2023)
    RUNX1 was not an independent prognostic factor for survival. Overall, our findings agree with the updated WHO classification system for AML that AML-RUNX1mut should not be recognized as a distinct AML entity.
    Retrospective data
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    TP53 mutation • FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • DNMT3A mutation • RUNX1 mutation • CEBPA mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation
    6ms
    Only FLT3-ITD Mutation Did Not Have a Deleterious Effect on Acute Myeloid Leukemia Patients with NPM1 Mutation, but Concomitant with DNMT3A Mutation or a<3log Reduction of MRD2 Predicted Poor Survival (ASH 2023)
    Patients were treated by an anthracycline and cytarabine-based or homoharringtonine and cytarabine-based induction chemotherapy regimen and followed by high dose cytarabine as consolidation therapy. A<3log reduction of MRD2 was also another independent poor prognostic factor for survival, which could be improved by allo-HSCT. Meanwhile, the conversion of MRD for NPM1 from negative to positive might be a poor prognostic factor, but it requires to be validated by multivariate analysis.
    Clinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation
    |
    cytarabine • Synribo (omacetaxine mepesuccinate)
    6ms
    Interaction between Presenting Features, Co-Occurring Mutations, MRD and Induction Treatment Influences Outcome in Adults with NPM1 Mutated AML – an Analysis of 1357 Patients in the UK NCRI AML17 and AML19 Studies (ASH 2023)
    Induction regimens included DA +/- etoposide (ADE) and FLAG-IDA, with or without Gemtuzumab. Conclusion The "triple hit" (NPM1, DNMT3A and FLT3 ITD) genotype, WT1mut and high WCC were associated with poor outcomes, due to a lower probability of achieving MRD–, and a higher relapse risk from MRD– remission. Survival was improved for patients receiving intensified induction with FLAG-Ida including patients in these high-risk groups.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • 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) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • WT1 (WT1 Transcription Factor)
    |
    TP53 mutation • KRAS mutation • FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation
    |
    etoposide IV • Mylotarg (gemtuzumab ozogamicin)
    11ms
    Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.
    Journal
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • 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) • TET2 (Tet Methylcytosine Dioxygenase 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    TP53 mutation • NRAS mutation • FLT3-ITD mutation • IDH1 mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • CEBPA mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation
    |
    decitabine
    over1year
    Identification of Novel Antigens for Normal Karyotype Triple Mutated Acute Myeloid Leukemia (ASH 2022)
    Patients with intermediate cytogenetic risk AML and high antigen expression show poor prognosis even after HSCT in first complete remission, highlighting the need to develop novel therapeutic strategies for these patients. Different immunotherapeutic approaches targeting these antigens are currently being developed by our group, with the hope of identifying novel therapeutic strategies for the treatment of NK triple mutated AML.
    IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • DNMT3A mutation • FLT3‐ITD + DNMT3A mutation
    2years
    Prognostic Relevance of DNMT3A, FLT3 and NPM1 Mutations in Syrian Acute Myeloid Leukemia Patients. (PubMed, Asian Pac J Cancer Prev)
    Patients with FLT3-ITD and NPM1 mutations have the worst prognosis, where the presence of those mutations was significantly related to overall survival (OS) and EFS. Our study reflects that DNMT3A was not an extremely bad prognostic effect as an independent factor. We can declare according to this study that genetic mutation and variants detection could easily be incorporated into the regimen evaluation of AML patients.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3 mutation + NPM1 mutation • FLT3‐ITD  + NPM1 mutation • FLT3‐ITD + DNMT3A mutation
    2years
    Prognostic impact of PRDM16 expression in acute myeloid leukemia with normal cytogenetics. (PubMed, Hematology)
    These data suggested PRDM16 expression could be used to predict the outcome of patients with CN-AML. PRDM16 is significantly associated with FLT3-ITD and DNMT3A mutation and WT1 expression and serves as a potential prognostic biomarker in CN-AML.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • DNMT3A (DNA methyltransferase 1) • WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PRDM16 (PR/SET Domain 16)
    |
    FLT3-ITD mutation • DNMT3A mutation • CEBPA mutation • DNMT3A mutation + FLT3-ITD mutation • WT1 mutation • FLT3‐ITD + DNMT3A mutation • MLL fusion
    over2years
    Prognostic Impact of Concurrent DNMT3A, FLT3 and NPM1 Gene Mutations in Acute Myeloid Leukemia Patients. (PubMed, Clin Lymphoma Myeloma Leuk)
    Our study supports adverse prognostic effect of presence of DNMT3A gene mutation either alone or in the presence of FLT3 and/or NPM1 gene mutations.
    Clinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation