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    BIOMARKER:

    FLT3-TKD 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
    Entrez ID:
    2322
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    Related tests:
    22d
    Molecular abnormalities and clinical features in adult patients with acute myeloid leukemia in Thailand. (PubMed, Diagn Pathol)
    The complexity of AML was influenced by various cytogenetic and molecular abnormalities, which contributed to patients' heterogeneous presentation and survival outcomes. In addition to the previous data, IDH1, IDH2, and DNMT3A mutations might have affected survival outcomes in AML patients in our retrospective cohort. However, further studies with larger sample sizes are needed to validate these observations.
    Journal
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    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) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • RAS (Rat Sarcoma Virus)
    |
    TP53 mutation • FLT3-ITD mutation • IDH1 mutation • FLT3 mutation • NPM1 mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • FLT3-TKD mutation • SRSF2 mutation
    2ms
    Long-term outcomes in FLT3-mutated acute myeloid leukemia after frontline hypomethylating agent, venetoclax and a FLT3 inhibitor. (PubMed, Haematologica)
    Triplet combinations of an HMA, venetoclax and a FLT3 inhibitor result in durable remission and encouraging long-term OS in older adults with newly diagnosed FLT3-mutated AML. However, better strategies to prevent FLT3 wild type relapses and to overcome RAS pathway-mediated resistance are still needed.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • RAS mutation • FLT3-TKD mutation
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    Venclexta (venetoclax)
    2ms
    Vyxeos Plus Gilteritinib in Relapsed or Refractory, FLT3-Mutated AML (clinicaltrials.gov)
    P1, N=22, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jan 2025 --> Feb 2027 | Trial completion date: May 2026 --> Mar 2027
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3-TKD mutation
    |
    Xospata (gilteritinib) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
    2ms
    Prevalence of Fms-Like Tyrosine Kinase 3 (FLT3) Mutations in Patients With Acute Myeloid Leukaemia: A Systematic Literature Review and Meta-Analysis. (PubMed, Cancer Med)
    We described the distribution of FLT3 mutations; further work is needed to understand prevalence estimate heterogeneity.
    Clinical • Retrospective data • Review • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
    4ms
    Outcomes of patients with newly diagnosed acute myeloid leukemia with FLT3-tyrosine kinase domain mutations: Prognostic implications of NPM1 co-mutation. (PubMed, Cancer)
    FLT3-TKDmut AML commonly harbors NPM1 co-mutation, which has key prognostic implications. Lack of NPM1 co-mutation portends a poor prognosis, and allogenic stem cell transplantation should be strongly considered for patients in first remission.
    Retrospective data • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3-TKD mutation
    |
    Venclexta (venetoclax)
    5ms
    Downregulation of S6 Kinase and Hedgehog-Gli1 by Inhibition of Fatty Acid Synthase in AML with FLT3-ITD Mutation. (PubMed, Int J Mol Sci)
    FASN inhibition resulted in reduced levels of phospho-Akt (pAkt) and phospho-S6 kinase (pS6) and decreased expression of Hedgehog-Gli1, confirming non-canonical regulation of Gli by FLT3-ITD signaling. Combining TVB-3166 with the Gli inhibitor GANT61 significantly reduced the survival of MOLM13 and MV411 cells.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • GLI1 (GLI Family Zinc Finger 1) • FASN (Fatty acid synthase)
    |
    FLT3-ITD mutation • FLT3-TKD mutation
    7ms
    Vyxeos Plus Gilteritinib in Relapsed or Refractory, FLT3-Mutated AML (clinicaltrials.gov)
    P1, N=22, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: May 2025 --> Jan 2025
    Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3-TKD mutation
    |
    Xospata (gilteritinib) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
    7ms
    Structural Optimization and MD Simulation Study of Benzimidazole Derivatives as Potent Mutant FLT3 Kinase Inhibitors Targeting AML. (PubMed, Arch Pharm (Weinheim))
    The molecular dynamics study of 4ACP and 22b was conducted to explain the significant changes in activity resulting from subtle structural alterations. Altogether, these findings establish 22b as a potent mutant FLT3 inhibitor, warranting further investigation and optimization to target resistant AML.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
    7ms
    Clinicopathological and global methylation profiling of acute myeloid leukemia with mutations in NPM1 and clonal hematopoiesis-related genes. (PubMed, Leuk Lymphoma)
    Additionally, despite variations in methylation profiles based on disease status, no distinct differences between DTA-positive and negative groups were observed. Notably, three probes, including one linked to the FAM65B promoter, effectively differentiated disease states, highlighting the potential role of FAM65B in leukemogenesis and patient survival.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
    |
    NPM1 mutation • TET2 mutation • FLT3-TKD mutation
    8ms
    Efficacy and safety analysis of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage (PubMed, Zhonghua Xue Ye Xue Za Zhi)
    All patients recovered hematopoietic function after the initial induction therapy, with no fatal hemorrhage, tumor lysis syndrome, neurological adverse events, or grade 3 or higher organ toxicity, excluding preexisting conditions. Venetoclax in combination with multidrug chemotherapy was effective and associated with tolerable adverse reactions in patients with newly diagnosed ALAL.
    Retrospective data • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
    |
    Venclexta (venetoclax)
    9ms
    Vyxeos Plus Gilteritinib in Relapsed or Refractory, FLT3-Mutated AML (clinicaltrials.gov)
    P1, N=22, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Jan 2025 --> May 2025
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3-TKD mutation
    |
    Xospata (gilteritinib) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
    10ms
    Genetic abnormalities predict outcomes in patients with core binding factor acute myeloid leukemia. (PubMed, Ann Hematol)
    In addition, increasing age, nonintensive chemotherapy, and high MRD levels predict poor outcomes in the RUNX1::RUNX1T1 cohort. In addition to the adverse impact of high KIT mutation burden and FLT3-ITD or FLT3-TKD mutations on prognosis in CBF-AML, KDM6A mutations predicted poor outcomes in patients with RUNX1::RUXN1T1; however, ASXL1 mutations, favourable outcomes; high mutation burden, poor outcomes in those with CBFB::MYH11.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • KDM6A (Lysine Demethylase 6A)
    |
    TMB-H • FLT3-ITD mutation • KIT mutation • ASXL1 mutation • FLT3-TKD mutation