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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
    12d
    Prognostic Significance of Low Copy Number FLT3 and NPM1 mrd As Detected By Ultra-Sensitive Next Generation Sequencing (ASH 2024)
    To our knowledge, our study is the first to assess the clinical impact of MRD detected below the clinically-validated limit of detection by ultra-sensitive NGS. Findings from our retrospective study were consistent with previously published data suggesting the presence of “high level” MRD (i.e. above the current clinically-validated limit of detection) is associated with increased risk of AML relapse in both NPM1 and FLT3-ITD mutated AML.
    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
    20d
    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
    7ms
    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
    12ms
    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
    12ms
    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
    1year
    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
    1year
    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
    1year
    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
    over1year
    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
    over1year
    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
    over1year
    EXPRESSION OF BCL2 , BAX AND MDR1 GENES AS PHARMACOTRANSCRIPTOMIC MARKERS OF PROGNOSIS IN DE NOVO PATIENTS OF ADULT ACUTE MYELOID LEUKEMIA WITH NORMAL KARYOTYPE (EHA 2023)
    This is the first study that focused only on AML-NK patients, when it comes to analysis of BCL2 , BAX and MDR1 gene expression profiles. The results of this preliminary study have shown that high BCL2 expression would likely lead to tumor resistance from chemotherapy, making anti-BCL2 treatment a viable option in patients with this expression profile. A study on a larger group of patients could clarify the prognostic importance of the studied pharmacotranscriptomics markers, contributing to a creation of personalized treatment of adult AML-NK patients.
    Clinical • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • BAX (BCL2-associated X protein)
    |
    FLT3-ITD mutation • NPM1 mutation • BCL2 overexpression • BCL2 expression • FLT3‐ITD  + NPM1 mutation • BAX expression • BAX underexpression
    over1year
    FIVE-YEAR REAL-WORLD DATA ON ACUTE MYELOID LEUKEMIA: RETROSPECTIVE STUDY FROM PUBLIC HEALTH CENTER IN BRAZIL (EHA 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 todiagnostic 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
    over1year
    THE INFLUENCE OF BCL2 , BAX , BAX/BCL2 RATIO AND MDR1 GENE EXPRESSION ON PROGNOSIS OF ADULT DE NOVO ACUTE MYELOID LEUKEMIA PATIENTS WITH NORMAL KARYOTYPE (EHA 2023)
    All patients received induction chemotherapy with daunorubicin and cytarabine (3+7) followed by three consolidation cycles of high/intermediate doses of cytarabine. Our analysis of BCL2 , BAX and MDR1 gene expression profiles is the first study focusing exclusively on AML-NK patients. Preliminary results showed that patients with high BCL2 expression are likely to be chemo resistant, and possibly may benefit from specific anti-BCL2 treatment. Further investigations conducted on a larger number of patients could elucidate actual prognostic significance of these genes in AML-NK patients.
    Clinical • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • BAX (BCL2-associated X protein)
    |
    FLT3-ITD mutation • NPM1 mutation • BCL2 expression • FLT3‐ITD  + NPM1 mutation • BAX expression
    |
    cytarabine • daunorubicin
    over1year
    Prognostic impact of FLT3-ITD, NPM1 mutation and CEBPA bZIP domain mutation in cytogenetically normal acute myeloid leukemia: a Hokkaido Leukemia Net study. (PubMed, Int J Hematol)
    Multivariate analysis showed that age < 65 years, FLT3-ITD and CEBPA bZIP in-frame mutation were independent prognostic factors. The results suggest that analyzing these gene mutations at diagnosis can inform selection of the optimal intensity of therapy for patients with CN-AML.
    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
    almost2years
    An NGS based MRD evaluation from acute myeloid leukemia patients. (PubMed, Int J Lab Hematol)
    The "AML NGS-MRD hot-spot panel" detected the mutations from relapsed AML patients with minimal panel size, and was a reliable and cost-effective panel for AML patients.
    Journal • Next-generation sequencing
    |
    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    KRAS mutation • NRAS mutation • FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    almost2years
    CD34 negative HLA-DR negative acute myeloid leukaemia: A higher association with NPM1 and FLT3-ITD mutations. (PubMed, Int J Lab Hematol)
    We found that the CD34 negative HLADR negative non APL AML is highly associated with NPM1 and FLT3-ITD mutation, older age at diagnosis, DIC, higher total leucocyte count, higher blast counts and normal karyotype in comparison to CD34 positive HLA-DR negative AML group. Co-occurrence of NPM1 and FLT3-ITD mutation was also exclusively seen in CD34 negative HLA-DR negative group. There was poor overall survival in CD34 positive HLA-DR negative AML than CD34 negative HLA-DR negative AML cases.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • CD34 (CD34 molecule)
    |
    FLT3-ITD mutation • NPM1 mutation • CD34 positive • FLT3‐ITD  + NPM1 mutation
    2years
    Prognostic Impact of NPM1 and FLT3-ITD Mutations in Patients Treated with Non-Intensive Regimens: A Pethema Registry Study (ASH 2022)
    Regarding the frontline therapy 328 (46.3%) patients received hypomethylating agents (HMA); 353 (49.9%) fludarabine + low dose cytarabine (LDAC) (FLUGA); 11 (1.6%) fludarabine + LDAC + oral idarubicin (FLAG-IDA Lite); and 15 (2.1%) LDAC...AML patients treated with azacitidine (N=281) had longer median OS of 10 months (p=0.005; 95% CI 1.03 to 1.37) vs decitabine (N=47) median OS 6.1 months and FLUGA median OS 5 months (N=352) (Fig... Data from this large cohort of AML patients treated with non-intensive regimens underlines the limitations of the ELN 2017 risk stratification in this setting. Nonetheless, there was a trend towards worse OS in patients with normal karyotype and FLT3-ITD mutation (irrespectively of the allelic burden) as compared to FLT3WT patients. Figure 1.
    Clinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3 wild-type • FLT3‐ITD  + NPM1 mutation
    |
    cytarabine • azacitidine • decitabine • idarubicin hydrochloride • fludarabine IV
    2years
    Conditioning Regimen Intensity and Donor Choice Do Not Impact Outcomes of Patients (pts) with Acute Myeloid Leukemia (AML) after Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) in First Complete Remission (CR1): An EBMT Analysis (ASH 2022)
    The most common conditioning regimen was fludarabine/busulfan in MSD (n=148, 50%), MUD (n=272, 57%) and MMUD (n=38, 43%) recipients, while thiotepa/fludarabine/busulfan was the most used in haplo-HCT (n=99, 60%)...Most (n=1002, 98%) pts received calcineurin inhibitors (CNI), tacrolimus or cyclosporine A, for graft-versus-host disease (GVHD) prophylaxis in addition to mycophenolate mofetil (43%) or methotrexate (38%). Post-transplant cyclophosphamide was used in 18% (n=191) of pts, with 71% (n=136) having received haplo-HCT, and anti-thymocyte globulin was given to 67% (n=689)...Survival after MSD allo-HCT is comparable to MUD and haplo, a finding that is in accordance with previous results for haplo and MUD as valid alternative donors in the absence of MSD. The use of MMUD was associated with lower OS compared to MSD and should be used as a last resort donor in this setting.
    Clinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3 wild-type • FLT3‐ITD  + NPM1 mutation
    |
    cyclophosphamide • methotrexate • fludarabine IV • thiotepa • busulfan • cyclosporin A microemulsion
    2years
    The Occurrence of Thrombosis during Intensive Chemotherapy Treatment for Acute Myeloid Leukemia Patients Does Not Impact on Long-Term Survival (ASH 2022)
    Leukemia-free survival was also comparable between groups (2.4 years versus 1 year; p=0.15). Conclusion Venous thrombosis is seen mostly during the initial induction phase of AML patients receiving intensive therapy with a tight association with the MRC intermediate risk category, however long-term survival and leukemia related outcomes are not significantly impacted by the diagnosis of thrombosis.
    Clinical
    |
    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
    2years
    Clinical and Functional Implications of MYC Variants As a New Class of Pathogenic Variants in AML (ASH 2022)
    Here we define MYC aberrations as a new class of pathogenic variants in childhood AML. We demonstrate functional and clinical characterization of a novel MYC-ITD and contrast this novel variant to that of established pathogenic MYCSNV/indel. We show the high prevalence of co-occurring core-binding factor fusions with MYC-ITD, and high frequency of co-occurring NUP98-NSD1, FLT3-ITD and NPM1 mutations in MYCSNV/indel.
    Clinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation • NUP98-NSD1 fusion
    2years
    Prognostic Relevance of NPM1 and FLT3 Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up-A Single Center Experience. (PubMed, Cancers (Basel))
    Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in NPM1-mutated patients both with the FLT3 wild-type and mutated AML, while in the NPM1 wild-type and FLT3-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3 mutation + NPM1 mutation • FLT3 wild-type • FLT3‐ITD  + NPM1 mutation
    |
    cytarabine • idarubicin hydrochloride
    over2years
    FLT3-ITD and NPM1 mutation positive acute myeloid leukemia with cuplike blasts mimicking acute promyelocytic leukemia (PubMed, Rinsho Ketsueki)
    The patient had no response to idarubicin combined cytarabine; however, qiuzartinib administration resulted in the first complete remission...She had a partial response to venetoclax combined with azacytidine, and qiuzartinib administration resulted in the first complete remission. Both cases were CD34- and HLA-DR-negative with disseminated intravascular coagulation mimicking acute promyelocytic leukemia (APL). Additionally, recognizing the cuplike blasts is useful to differentiate FLT3 mutant AML from APL for the proper use of FLT3 inhibitors.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • CD33 (CD33 Molecule) • CD34 (CD34 molecule)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • CD33 positive • FLT3‐ITD  + NPM1 mutation
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • idarubicin hydrochloride
    over2years
    Characteristics and outcome of patients with acute myeloid leukemia and trisomy 4. (PubMed, Haematologica)
    In our cohort, patients with trisomy 4 as a sole abnormality had a high CR rate and favorable clinical outcome. Allo-HCT seems not to improve OS.
    Clinical • 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
    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
    over2years
    Platelet to white blood cell ratio was an independent prognostic predictor in acute myeloid leukemia. (PubMed, Hematology)
    Finally, PWR was associated with favorable overall survival and event free survival in CN-AML patients independent of genetic subtypes and clinical parameters. We found PWR was an independent prognostic predictor in CN-AML.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • CEBPA mutation • FLT3‐ITD  + NPM1 mutation
    almost3years
    TERT genetic variability and telomere length as factors affecting survival and risk in acute myeloid leukaemia. (PubMed, Sci Rep)
    Patients with adverse risk classification (mutation in FLT3-ITD and lack of mutation in NPM1) presented with the shortest telomeres and significantly worse OS. In conclusion, OS of AML patients appears to be affected by TERT gene variability and TL in addition to other well-established factors such as age, WBC count, or FLT3-ITD and NPM1 mutation status.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • TERT (Telomerase Reverse Transcriptase)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • TERT mutation • FLT3‐ITD  + NPM1 mutation
    almost3years
    AUTOLOGOUS VERSUS HAPLOIDENTICAL STEM CELL TRANSPLANTATION IN ADULT PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA IN FIRST REMISSION WITH UNDETECTABLE MINIMAL RESIDUAL DISEASE: A EUROPEAN PRELIMINARY ANALYSIS: (EBMT 2022)
    In the autografted population the myeloablative conditioning (MAC) consisted essentially (69%) of the combination of busulfan + cyclophosphamide or busulfan + high-dose melphalan.  For adult patients with AML with uMRD-CR1, Haplo with PTCY resulted in a superior LFS of 65% versus 50% at 3 years and a GRFS of 54%. By intention to treat there was no difference for OS.
    Clinical • Minimal residual disease
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    cyclophosphamide • melphalan • busulfan
    almost3years
    'FLT3-ITD Mutation Does Not Influence Survival Outcome in Adult Acute Promyelocytic Leukemia Patients Treated With ATO and ATRA-Based Therapeutic Regimen: Experience From a North Indian Tertiary Care Centre'. (PubMed, Clin Lymphoma Myeloma Leuk)
    FLT3-ITD mutation did not influence survival outcome in adult APL treated with ATO and ATRA-based therapeutic regimen.
    Clinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • BCR (BCR Activator Of RhoGEF And GTPase) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    Vesanoid (tretinoin)
    3years
    Prediction of Early Mortality with Non-Intensive Acute Myeloid Leukemia (AML) Therapies: Analysis of 1336 Patients from MRC/NCRI and SWOG (ASH 2021)
    Treatments included: Low dose Ara-C (LDAC) alone, sapacitabine alone and LDAC in combination with vosaroxin, tosedostat or ganetespib (MRC/NCRI); Azacytidine (AZA) alone, tipifarnib alone, and AZA in combination with mylotarg, midostaurin, and nivolumab (SWOG). Our ability to predict early death in older patients treated with lower intensity AML therapies is limited with routinely available clinical variables. Inclusion of cytogenetic risk, FLT3-ITD, and NPM1 mutation status minimally improved the prognostic accuracy as did some of the QLQ-C30 subscales. Our data highlight the difficulties in predicting outcomes with non-intensive AML therapy with routinely available baseline clinical information.
    Clinical • PD(L)-1 Biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    Opdivo (nivolumab) • cytarabine • azacitidine • Rydapt (midostaurin) • Zarnestra (tipifarnib) • Mylotarg (gemtuzumab ozogamicin) • ganetespib (ADX-1612) • Qinprezo (vosaroxin) • sapacitabine (CYC682) • tosedostat (CHR-2797)
    3years
    Mutation profile of acute myeloid leukaemia in a Chinese cohort by targeted next-generation sequencing. (PubMed, Cancer Rep (Hoboken))
    Both DNMT3A and NPM1 mutations were more common than in other Chinese and Western AML cohorts that have been studied. DNMT3A mutations tended to co-occur with NPM1 and FLT3-ITD mutations and were most commonly seen with a normal karyotype.
    Journal • Next-generation sequencing
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • FLT3‐ITD  + NPM1 mutation
    3years
    Acute myeloid leukemia with cup-like blasts and FLT3-ITD and NPM1 mutations mimics features of acute promyelocytic leukemia: a case of durable remission after sorafenib and low-dose cytarabine. (PubMed, Anticancer Drugs)
    He had no response to both arsenic trioxide and CAG regimen (cytarabine, aclarubicin, and G-CSF). To date, the patient achieved durable complete remission over 58 months. These findings suggest that AML with cup-like blasts and FLT3-ITD and NPM1 mutations mimic APL, and the prognosis of this subtype may be improved by sorafenib combined with LDAC.
    Clinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • CD34 (CD34 molecule)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    sorafenib • cytarabine • arsenic trioxide • aclarubicin
    3years
    The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia. (PubMed, Mol Biol Rep)
    TNFRSF4 expression was revealed as an unfavorable prognostic marker and might be a target for immunotherapy in the future.
    Journal • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • TNFRSF4 (TNF Receptor Superfamily Member 4)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation • TNFRSF4 expression
    3years
    Maturation State-Specific Alternative Splicing in FLT3-ITD and NPM1 Mutated AML. (PubMed, Cancers (Basel))
    Interestingly, we observed functional divergence between alternatively spliced and differentially expressed genes in FLT3-ITD+/NPM1+ samples in all analyzed FAB types, with differential expression affecting genes involved in hematopoietic differentiation. Altogether, these observations indicate that concomitant FLT3-ITD and mutated NPM1 are associated with the maturation state-specific differential splicing of genes with potential oncogenic relevance.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation • FLT3 expression • FLT3-ITD expression
    over3years
    Molecular characterisation of NPM1 and FLT3-ITD mutations in a central South African adult de novo acute myeloid leukaemia cohort. (PubMed, Afr J Lab Med)
    High FLT3-ITD allele ratios and long ITD lengths predominated. No NPM1 mutations were detected.
    Clinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    over3years
    [VIRTUAL] SUPERIOR OUTCOMES FOLLOWING ALLOGENEIC STEM CELL TRANSPLANTATION IN FIRST REMISSION FOR NPM1/FLT3-ITD MUTATED AML (EHA 2021)
    Importantly, 52% (n=14) of FLT3-ITD-ve cases achieved a second remission (CR2) with chemotherapy, while only 24% (n=5) of FLT3-ITD+ cases were able to reach CR2 (p=0.049 [data precede availability of Gilteritinib at relapse])...Significantly higher relapse rates were observed in FLT3-ITD+ cases treated with chemotherapy alone, followed by poor responses to salvage chemotherapy and fewer patients achieving CR2. Collectively, our data suggest that alloSCT consolidation should be prioritised in NPM1+/FLT3-ITD+ AML to achieve improved long-term outcomes within this higher risk cohort.
    Clinical
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation
    |
    Xospata (gilteritinib)
    over3years
    Erythroleukemia: an Update. (PubMed, Curr Oncol Rep)
    Hypomethylating agents have shown therapeutic value in AEL. In this article, we discuss the evolving diagnostic concepts of erythroleukemia, genomics, clinical outcome, and promising therapeutic targets through an appraisal of the current literature.
    Review • Journal
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    TP53 mutation • FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD  + NPM1 mutation