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    BIOMARKER:

    FLT3‐ITD  + NPM1 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, 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:
    2322; 4869
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    1year
    Prognostic Significance of Low Copy Number FLT3 and NPM1 mrd As Detected By Ultra-Sensitive Next Generation Sequencing (ASH 2024)
    While most patients with "low-level" MRD positivity later have negative MRD testing, there is a subset of patients that go on to develop "high-level" MRD and are thus at increased risk of relapse. These data suggest that MRD positivity below the clinically-validated limit of detection is challenging to interpret, and that longitudinal MRD monitoring is vital for disease surveillance.
    Next-generation sequencing
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    FLT3 ITD MRD Assay • NPM1 Mutation Assay
    1year
    Exploring the Prevalence and Prognostic Impact of Wilms Tumor 1 Exon 7 Mutation Status with Combinations of FLT3-ITD and NPM1 Mutations as Potential Molecular Biomarkers in Acute Myeloid Leukemia Patients with Normal Cytogenetics. (PubMed, Asian Pac J Cancer Prev)
    This study found a significant association between patient survival outcomes and NPM1 mutation status, as well as the combined FLT3-ITD and NPM1 status. Profiling both NPM1 and FLT3-ITD mutations at the time of diagnosis serves as a robust prognostic marker in AML treatment. WT1 mutation status did not show a significant association with patient outcomes. Larger population studies may provide more relevant insights.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)
    |
    FLT3-ITD mutation • NPM1 mutation • WT1 mutation • FLT3‐ITD  + NPM1 mutation • FLT3-ITD mutation + WT1 mutation • FLT3‐ITD + WT1 mutation
    over1year
    Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study. (PubMed, Br J Haematol)
    Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.
    Retrospective data • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    2years
    Molecular Characterisation and Outcomes of 363 Adolescent and Young Adults with AML in Saudi Arabia Risk Stratified By PCR and NGS-Based Testing (ASH 2023)
    The study presents the largest molecular profiling to our knowledge of this population. The study emphasises the need for integration of NGS to enhance risk stratification and precision, enable better characterisation of high-risk patients, and improve the potential for targeted treatments.
    Clinical • Next-generation sequencing
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    FLT3-ITD mutation • NPM1 mutation • KIT mutation • ASXL1 mutation • CEBPA mutation • FLT3‐ITD  + NPM1 mutation
    2years
    Five-Year Real World Data on AML Retrospective Study from Public Health Center in Brazil (ASH 2023)
    The standard remission induction regimen for medically eligible patients with AML consists of a backbone of cytarabine & an anthracycline (“7+3” therapy)... The outcomes were consistent with the literature, adjusted for the population in question. Even with access to diagnostic tests (not common in Brazilian's health public centers), patients did not have access to targeted therapies, with the 7+3 regimen being the only treatment for fit patients. To achieve complete remission followed consolidation/transplantation is still the BEST scenarios in AML eligible patients, but the improvement of access to diagnostic and treatment is still an unmet need.
    Retrospective data • Real-world evidence • Real-world
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    cytarabine
    2years
    GILTERITINIB MONOTHERAPY AS A TRANSPLANT BRIDGING OPTION FOR HIGH RISK FLT3-MUTATED NPM1 MUTATED AML IN MORPHOLOGICAL BUT NOT MOLECULAR REMISSION FOLLOWING STANDARD INDUCTION AND SAVAGE THERAPY (SIE 2023)
    The patient started cytoreductive therapy with hydroxyurea but after recovery from the SARS COV2 infection, presented cutaneous nodularities, jet vomiting, eyelid ptosis and decreased visual acuity...She started induction chemotherapy 3+7 regimen plus anti-CD33 gemtuzumab-ozogamicin therapy and medicated lumbar punctures with cytarabine...The patient was started to pretransplantation work up but unfortunately a cytomegalic infection complicated by acute heart failure led to the death of the patient. In conclusion, this case report points out some effects of Gilteritinib: the potential utility of FLT3 inhibitors in relapsed AML patients, the safe administration, the efficacy of gilteritinib monotherapy also as a bridge to transplantation, the ability to clearance blast percentage in a short period of time.
    Clinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    cytarabine • Xospata (gilteritinib) • Mylotarg (gemtuzumab ozogamicin) • hydroxyurea
    2years
    The Impact of DNMT3A Mutation on Survival of AML Patients Receiving Allogeneic Hematopoietic Cell Transplantation in First Remission Depends on the Karyotype and Co-Occurring Mutations: On Behalf of the EBMT Acute Leukemia Working Party (ASH 2023)
    Our data suggest that DNMT3A mutation negatively affects post-transplant survival selectively in patients with normal karyotype and either NPM1 mutation without FLT3-ITD, or patients with normal karyotype, FLT3-ITD and wild type NPM1. DNMT3A mutation shows no impact on post-transplant outcomes in other settings.
    Clinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • FLT3 wild-type • FLT3‐ITD  + NPM1 mutation
    2years
    Characterization of the Molecular Landscape of Pediatric Acute Myeloid Leukemia: A Retrospective AIEOP AML2013/01 Study (ASH 2023)
    Overall, in the prospective AIEOP AML2013/01 trial, we described the frequency of different molecular lesions and improved the genetic landscape of AML. The future use of NGS-based screenings could further optimize the characterization of the genetic landscape of childhood AML, thus refining the risk class patients stratification and modulation of treatment approaches.
    Retrospective data
    |
    FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • WT1 (WT1 Transcription Factor) • CREBBP (CREB binding protein) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NUP214 (Nucleoporin 214) • FUS (FUS RNA Binding Protein) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2) • KAT6A (Lysine Acetyltransferase 6A) • KDM5A (Lysine Demethylase 5A) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor) • RBM15 (RNA Binding Motif Protein 15)
    |
    FLT3-ITD mutation • NPM1 mutation • KIT mutation • CEBPA mutation • WT1 mutation • FLT3‐ITD  + NPM1 mutation • MLL fusion
    over2years
    Cytogenetically Normal Acute Myeloid Leukaemia at a Single Centre in South Africa. (PubMed, Hematol Oncol Stem Cell Ther)
    Local rates of CN-AML and associated NPM1 and FLT3-ITD mutations were comparable to those of European cohorts. Limited mutation analysis in the form of triple-mutation testing proved to be an economical and therapeutically informative prognostication approach for CN-AML in a resource-limited setting.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    FLT3-ITD mutation • NPM1 mutation • CEBPA mutation • FLT3‐ITD  + NPM1 mutation
    over2years
    COMPARISON OF CLINICAL CHARACTERISTICS OF ADULT CHILEAN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML), ACCORDING TO THEIR HEALTH CARE SYSTEM: ANALYSIS WITHIN THE FRAMEWORK OF THE PTHEMA AML REGISTRY (EHA 2023)
    Overall, 64.6% of the patients received induction chemotherapy (79% private vs 60.2% public, p 60 years. Adult, Acute myeloid leukemia, Clinical data
    Clinical • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    cytarabine