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    BIOMARKER:

    FLT3-ITD 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:
    2d
    The potential of triplet combination therapies for patients with FLT3-ITD -mutated acute myeloid leukemia. (PubMed, Expert Rev Hematol)
    In addition, the review discusses the emergence of drug resistance and the need for a nuanced approaches in treating patients who are ineligible for or resistant to intensive chemotherapy. Specifically, it explores the historical context of FLT3 inhibitors (FLT3Is) and their impact on treatment outcomes, emphasizing the pivotal role of midostaurin, as well as gilteritinib and quizartinib, and providing detailed insights into ongoing trials exploring the safety and efficacy of novel triplet combinations involving FLT3Is in different AML settings.
    Review • Journal • Combination therapy
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation
    |
    Xospata (gilteritinib) • Rydapt (midostaurin) • Vanflyta (quizartinib)
    3d
    DETECTION OF MEASURABLE RESIDUAL DISEASE IN AML BY NEXT-GENERATION SEQUENCING: INITIAL EXPERIENCES AND BENCHMARKING OF THE SURESEQ MYELOID MRD PANEL (EHA 2024)
    This initial evaluation of the SureSeq Myeloid MRD Panel for MRD detection in AML patients undergoingallogeneic HSCT demonstrates the assay has high analytical sensitivity, including detection of FLT3-ITDmutations which are emerging as a clinically relevant MRD marker, and is broadly applicable to a diversepopulation of AML patients undergoing allogeneic HSCT. Prospective analyses of the clinical relevance of NGS-based MRD measurements are ongoing.
    Next-generation sequencing
    |
    FLT3 (Fms-related tyrosine kinase 3) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
    |
    FLT3-ITD mutation
    |
    SureSeq™ Myeloid MRD Panel
    3d
    LLS 2024 ELN-REFINED RISK STRATIFICATION IN OLDER ADULTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA TREATED WITH LOW-INTENSITY THERAPY (EHA 2024)
    Among patients ≥60 yrs with ND AML given LIT, the current 2022 ELN risk system classifies most (79%)patients as adverse risk and does not reliably distinguish favorable from intermediate-risk, highlighting thelimitations of the model in this patient population. We propose a refined LLS classification using a "mutationscore" incorporating IDH2, MLL2, KRAS and TP53 mutations for those previously assigned ELN 2022 adverserisk, as well as redefining the definition of LLS-favorable risk.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • KMT2D (Lysine Methyltransferase 2D) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2)
    |
    TP53 mutation • KRAS mutation • FLT3-ITD mutation • IDH2 mutation • FLT3 mutation • KMT2D mutation • TP53 mutation + KRAS mutation • MLL2 mutation • KRAS mutation + TP53 mutation
    |
    FoundationOne® Heme CDx • LeukoStrat® CDx FLT3 Mutation Assay
    3d
    THE CLINICAL IMPACT OF CONCURRENT GENE MUTATIONS AND CYTOGENETIC ABNORMALITIES ON NPM1-MUTATED AML: A RETROSPECTIVE COHORT STUDY OF 1,520 PATIENTS (EHA 2024)
    NPM1 mutations were identified in 21. 7% of 1,520 patients. Patients with NPM1mut were older and had higherWBC counts and LDH levels, and more often had a normal karyotype, but less adverse cytogenetic features,including monosomal karyotype and MR cytogenetic abnormalities at diagnosis compared to NPM1wtpatients.
    Retrospective data
    |
    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) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    TP53 mutation • FLT3-ITD mutation • IDH1 mutation • FLT3 mutation • NPM1 mutation • DNMT3A mutation • TET2 mutation • KMT2A-PTD
    |
    TruSight Myeloid Sequencing Panel
    9d
    Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients. (PubMed, Ann Hematol)
    No significant difference was observed in OS and EFS between patients with NPM1A - type mut and NPM1non - A-type mut. However, types of NPM1 mutations and the status of FLT3-ITD mutations may jointly have an impact on the prognosis of AML patients.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
    |
    FLT3-ITD mutation • NPM1 mutation
    12d
    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
    12d
    FLT3-Selective PROTAC: Enhanced Safety and Increased Synergy with Venetoclax in FLT3-ITD Mutated Acute Myeloid Leukemia. (PubMed, Cancer Lett)
    Gilteritinib, used as the ligand for the target protein, was connected with different E3 ligase ligands to synthesize several series of PROTAC targeting FLT3-ITD. The FLT3-selective PROTAC can mitigate the platelet toxicity of small molecule inhibitors, ensuring safety and efficacy in monotherapy and combination therapy with Venetoclax. It is a promising strategy for FLT3-ITD+ patients, especially those with platelet deficiency or liver damage.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    |
    Venclexta (venetoclax) • Xospata (gilteritinib)
    16d
    Emerging DNA Methylome Targets in FLT3-ITD-Positive Acute Myeloid Leukemia: Combination Therapy with Clinically Approved FLT3 Inhibitors. (PubMed, Curr Treat Options Oncol)
    Hence, FLT3 is considered an attractive druggable target; selective small FLT3 inhibitors (FLT3Is), such as midostaurin and quizartinib, have been clinically approved. Therefore, understanding the role of different epigenetic alterations in FLT3-ITD AML pathogenesis and how they modulate FLT3I's activity is important to rationalize combinational treatment approaches including FLT3Is and modulators of methylation regulators or pathways. Data from ongoing pre-clinical and clinical studies will further precisely define the potential use of epigenetic therapy together with FLT3Is especially after characterized patients' mutational status in terms of FLT3 and DNA methlome regulators.
    Review • Journal • Combination therapy
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
    |
    FLT3-ITD mutation
    |
    Rydapt (midostaurin) • Vanflyta (quizartinib)
    17d
    Molecular, clinical and therapeutic determinants of outcome in NPM1 mutated AML. (PubMed, Blood)
    However, apart from the few patients with adverse cytogenetics, we could not identify any group of MRD negative patients with a CIR >40% or with benefit from allograft in first remission. Intensified chemotherapy with the FLAG-Ida regimen was associated with improved outcomes in all subgroups, with greater benefits observed in the highest risk molecular subgroups.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • WT1 (WT1 Transcription Factor)
    |
    FLT3-ITD mutation • NPM1 mutation
    22d
    FLT3 and IRAK4 Inhibitor Emavusertib in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia. (PubMed, Curr Issues Mol Biol)
    The FLT3 and IRAK4 inhibitor emavusertib (CA4948), the MCL1 inhibitor S63845, the BCL2 inhibitor venetoclax, and the HSP90 inhibitor PU-H71 were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells in vitro. The combination of CA4948 and BH3-mimetics may be effective in the treatment in FLT3-mutated AML with differential target specificity for MCL1 and BCL2 inhibitors. Moreover, the combination of CA4948 and PU-H71 may be a candidate combination treatment in FLT3-mutated AML.
    Journal • Combination therapy • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • CD34 (CD34 molecule) • ITGAM (Integrin, alpha M) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation
    |
    Venclexta (venetoclax) • S63845 • emavusertib (CA-4948) • zelavespib intravenous (PU-H71 IV)
    23d
    Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors. (PubMed, J Med Chem)
    Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • CD33 (CD33 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
    |
    FLT3-ITD mutation
    24d
    Narazaciclib, a novel multi-kinase inhibitor with potent activity against CSF1R, FLT3 and CDK6, shows strong anti-AML activity in defined preclinical models. (PubMed, Sci Rep)
    Significant leukemia load reductions in bone marrow, where disease originated, were also achieved in both responders (AM7577/AM8096), implicating that HX301 might be a potentially more effective therapy than those only affecting peripheral leukemic cells. Altogether, narazaciclib can potentially be a candidate treatment for a subset of AML with CSF1Rhi and/or mutant FLT3-ITD variants, particularly second generation FLT3 inhibitor resistant variants.
    Preclinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • CDK6 (Cyclin-dependent kinase 6) • CSF1R (Colony stimulating factor 1 receptor)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3 wild-type
    |
    narazaciclib (HX301)
    25d
    Cost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia. (PubMed, Leuk Lymphoma)
    With an incremental gain of 0.84 quality-adjusted life years (QALYs) with quizartinib + 7 + 3 induction vs. 7 + 3 alone, the incremental cost-effectiveness ratio for the addition of quizartinib to standard 7 + 3 was $344,039/QALY. Only an 87% reduction in the average wholesale price of quizartinib or omitting quizartinib continuation therapy after completion of consolidation therapy and allogeneic hematopoietic cell transplant would make quizartinib a cost-effective option.
    Journal • HEOR • Cost-effectiveness • Cost effectiveness
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    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation
    |
    Vanflyta (quizartinib)
    28d
    Current knowledge about FLT3 gene mutations, exploring the isoforms, and protein importance in AML. (PubMed, Mol Biol Rep)
    This review also discusses the development of molecular treatments targeting FLT3, including first-generation and next-generation tyrosine kinase inhibitors, highlighting the challenges of resistance that often arise during therapy. The final chapter describes FLT3 protein domain rearrangements and their relevance to AML pathogenesis.
    Review • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
    1m
    Inhibition of NRF2 signaling overcomes acquired resistance to arsenic trioxide in FLT3-mutated Acute Myeloid Leukemia. (PubMed, Ann Hematol)
    We have previously reported that primary cells from FLT3-ITD mutated AML patients were sensitive to ATO in-vitro compared to other non-M3 AML and molecular/pharmacological inhibition of NF-E2 related factor 2 (NRF2), a master regulator of antioxidant response improved the chemosensitivity to ATO and daunorubicin even in non FLT3-ITD mutated cell lines and primary samples. We examined the effects of molecular/pharmacological suppression of NRF2 on acquired ATO resistance in the FLT3-ITD mutant AML cell line (MV4-11-ATO-R). Digoxin decreased leukemic burden and prolonged survival in MV4-11 ATO-R xenograft mice. We establish that altering NRF2 expression may reverse acquired ATO resistance in FLT3-ITD AML.
    Preclinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • GLI2 (GLI Family Zinc Finger 2)
    |
    FLT3-ITD mutation • FLT3 mutation
    |
    daunorubicin • arsenic trioxide
    1m
    Myeloid neoplasms in inflammatory bowel disease: A case series and review of the literature. (PubMed, Leuk Res Rep)
    No IBD characteristic was found to associate with MN disease severity, including the previously-identified association between MNs and thiopurine exposure. Of the somatic mutations identified in out cohort's MN, mutations in TET2 were most prevalent, followed by FLT3-ITD, BCR-ABL, and NPM1 mutations.
    Review • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NPM1 (Nucleophosmin 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
    |
    FLT3-ITD mutation • NPM1 mutation • TET2 mutation
    1m
    Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine. (PubMed, Cancer Pathog Ther)
    Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.
    Journal • Next-generation sequencing
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • GATA2 (GATA Binding Protein 2)
    |
    FLT3-ITD mutation • IDH1 mutation • PTPN11 mutation
    |
    cytarabine • decitabine • aclarubicin
    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
    2ms
    Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance (clinicaltrials.gov)
    P2, N=107, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    FLT3-ITD mutation • NPM1 mutation • CEBPA mutation
    |
    cytarabine • Rydapt (midostaurin)
    2ms
    Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency. (PubMed, Front Immunol)
    Together, our data suggests that FLT3-ITD+ leukemia-associated cDCs polarize CD4+ T cells into Th17 subsets, a population that has been shown to be negatively associated with survival in solid tumor contexts. This illustrates the complex tumor microenvironment of AML and highlights the need for further investigation into the effects of FLT3-ITD mutations on DC phenotypes and their downstream effects on Th polarization.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • CD4 (CD4 Molecule) • CDK1 (Cyclin-dependent kinase 1)
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    FLT3-ITD mutation • FLT3 mutation
    2ms
    Genetic alterations in myeloid sarcoma among acute myeloid leukemia patients: insights from 37 cohort studies and a meta-analysis. (PubMed, Front Oncol)
    This meta-analysis sheds light on the prevalence of genetic mutations in AML patients with MS, providing insights into the unique characteristics of the mutations and their frequencies. These discoveries are crucial in informing therapeutic and prognostic decisions for individuals with myeloid sarcoma.
    Retrospective data • Review
    |
    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    NRAS mutation • FLT3-ITD mutation • IDH2 mutation • CEBPA mutation
    2ms
    NCI-2019-04959: Azacitidine, Venetoclax, and Gilteritinib in Treating Patients With Recurrent/Refractory FLT3-Mutated Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or High-Risk Myelodysplastic Syndrome/Myeloproliferative Neoplasm (clinicaltrials.gov)
    P1/2, N=55, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=42 --> 55
    Enrollment closed • Enrollment change
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3 D835
    |
    Venclexta (venetoclax) • Xospata (gilteritinib)
    2ms
    GOSSAMER: A Study of ASP2215 (Gilteritinib), Administered as Maintenance Therapy Following Induction/Consolidation Therapy for Subjects With FMS-like Tyrosine Kinase 3 (FLT3/ITD) Acute Myeloid Leukemia (AML) in First Complete Remission (clinicaltrials.gov)
    P2, N=98, Completed, Astellas Pharma Global Development, Inc. | Active, not recruiting --> Completed
    Trial completion
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    |
    Xospata (gilteritinib)
    2ms
    Paclitaxel mediates the PI3K/AKT/mTOR pathway to reduce proliferation of FLT3‑ITD+ AML cells and promote apoptosis. (PubMed, Exp Ther Med)
    The present study used the CCK-8 assay, flow cytometry, PCR and western blotting to explore the anti-leukemia effect and possible mechanisms of PTX on MV4-11 cells with the FLT3-ITD mutation and the underlying mechanism. As a result, it was found that PTX could inhibit proliferation of MV4-11 cells and promoted apoptosis by inhibiting the PI3K/AKT/mTOR pathway.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    |
    paclitaxel
    2ms
    Gilteritinib as Post-Transplant Maintenance for Acute Myeloid Leukemia With Internal Tandem Duplication Mutation of FLT3. (PubMed, J Clin Oncol)
    Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.
    Journal • Post-transplantation
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation
    |
    Xospata (gilteritinib)
    2ms
    Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene (clinicaltrials.gov)
    P1, N=28, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Feb 2024 --> Dec 2027 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2024 --> Dec 2027
    Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation
    |
    daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)
    2ms
    FLT3-ITD mutation-positive acute myeloid leukemia undergoing clonal transition with PTPN11 mutation at relapse (PubMed, Rinsho Ketsueki)
    The patient received gilteritinib monotherapy and achieved CR...He underwent related haploidentical peripheral blood stem cell transplantation but died of relapse. This was a case in which genetic analysis revealed clonal transition and acquisition of resistance to treatment.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    FLT3-ITD mutation • PTPN11 mutation
    |
    Xospata (gilteritinib)
    2ms
    Outcomes and prognosis of haploidentical haematopoietic stem cell transplantation in children with FLT3-ITD mutated acute myeloid leukaemia. (PubMed, Bone Marrow Transplant)
    The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 35.6% ± 5.2%, and that of grade III-IV aGVHD was 15.6% ± 3.0% The overall 4-year cumulative incidence of chronic graft-versus-host disease after transplantation was 35.7% ± 9.8%, respectively. In conclusion, haplo-HSCT may be a feasible strategy for paediatric patients with FLT3-ITD AML, and pre-HSCT MRD status and NR after introduce 1 significantly affected the outcomes.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    2ms
    A comprehensive genomic profiling of myeloid malignancies demonstrates mutational spectrum of DNA variants, FLT3-ITDs, and gene fusions (AACR 2024)
    The Oncomine Myeloid Assay is a fast, robust, and reproducible solution for comprehensive genomic profiling of myeloid malignancies. We describe the mutational spectrum of DNA variants and RNA fusions in a range of clinical research samples. (For research use only.
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • DNMT3A (DNA methyltransferase 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CREBBP (CREB binding protein) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • ZMYM2 (Zinc Finger MYM-Type Containing 2) • CALR (Calreticulin) • KAT6A (Lysine Acetyltransferase 6A) • ANKRD26 (Ankyrin Repeat Domain Containing 26)
    |
    FLT3-ITD mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • FGFR1 fusion
    |
    Oncomine Myeloid Assay GX • Oncomine Myeloid Research Assay
    2ms
    Reduced toxicity (FluBu3) versus myeloablative (BuCy) conditioning in acute myeloid leukemia patients who received first allogeneic hematopoietic stem cell transplantation in measurable residual disease-negative CR1. (PubMed, Bone Marrow Transplant)
    The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    3ms
    Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial) (clinicaltrials.gov)
    P2, N=153, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RARA (Retinoic Acid Receptor Alpha) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • PML (Promyelocytic Leukemia) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    TP53 mutation • FLT3-ITD mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • FLT3-TKD mutation • CEBPA mutation
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • Starasid (cytarabine ocfosfate)
    3ms
    Venetoclax with decitabine or azacitidine in relapsed or refractory acute myeloid leukemia. (PubMed, Med Oncol)
    The addition of venetoclax, a BCL-2 antagonist, to lower-intensity therapies results in improved survival in the first-line setting compared to monotherapy with a hypomethylating agent or low-dose cytarabine. Using an incremental survival computation method, we discovered that a CCI score threshold of 5 distinguishes patients at an elevated risk of death. Together, these novel findings highlight areas of refinement to improve survival in relapsed or refractory AML.
    Journal • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1)
    |
    KRAS mutation • NRAS mutation • FLT3-ITD mutation • NPM1 mutation
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • decitabine
    3ms
    Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques. FLT3-ITD, RUNX1, ASXL1 or TP53 mutation indicates a worse prognosis, but further clinical studies are needed to confirm it.
    Journal
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia) • CD34 (CD34 molecule) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • CD68 (CD68 Molecule) • CBFB (Core-Binding Factor Subunit Beta 2) • CD99 (CD99 Molecule) • SPN (Sialophorin)
    |
    TP53 mutation • FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • KIT mutation • ASXL1 mutation • CEBPA mutation
    3ms
    A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia. (clinicaltrials.gov)
    P1/2, N=84, Active, not recruiting, Astellas Pharma Inc | Trial completion date: Dec 2024 --> Jul 2024
    Trial completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    |
    cytarabine • Xospata (gilteritinib) • idarubicin hydrochloride
    3ms
    Cellular hierarchy insights reveal leukemic stem-like cells and early death risk in acute promyelocytic leukemia. (PubMed, Nat Commun)
    Finally, we show that ATRA induces differentiation of primitive blasts and patients with early death exhibit distinct stemness-associated transcriptional programs. Our work provides a thorough survey of APL cellular hierarchies, offering insights into cellular dynamics during targeted therapy.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia)
    |
    FLT3-ITD mutation
    3ms
    Study of NMS-03592088 in Patients With Relapsed or Refractory AML or CMML (clinicaltrials.gov)
    P1/2, N=200, Recruiting, Nerviano Medical Sciences | N=140 --> 200 | Trial completion date: Sep 2023 --> Feb 2026 | Trial primary completion date: Sep 2023 --> Dec 2025
    Enrollment change • Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    |
    NMS-088
    3ms
    Phase II Study of Crenolanib in Subjects With Relapsed/Refractory AML With FLT3 Activating Mutations (clinicaltrials.gov)
    P2, N=14, Completed, Arog Pharmaceuticals, Inc. | N=20 --> 14
    Enrollment change
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    |
    crenolanib (ARO-002)
    3ms
    IMPACT OF CO-MUTATIONS ON THE TRANSPLANT OUTCOMES IN AML PATIENTS WITH DNMT3A MUTATION (EBMT 2024)
    Notably, none of the patients received oral azacitidine as maintenance therapy... The results indicated that NPM1-/FLT3-ITD- and NPM1+/FLT3-ITD- subgroups in DNMT3A mutated AML benefit from allo-HSCT in CR1. Larger cohorts are warranted to validate these findings.
    Clinical
    |
    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) • ASXL1 (ASXL Transcriptional Regulator 1)
    |
    FLT3-ITD mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation
    |
    TruSight Myeloid Sequencing Panel
    |
    Onureg (azacitidine oral)
    3ms
    IMPACT OF CO-MUTATIONS ON THE TRANSPLANT OUTCOMES IN AML PATIENTS WITH DNMT3A MUTATION (EBMT 2024)
    Notably, none of the patients received oral azacitidine as maintenance therapy... The results indicated that NPM1-/FLT3-ITD- and NPM1+/FLT3-ITD- subgroups in DNMT3A mutated AML benefit from allo-HSCT in CR1. Larger cohorts are warranted to validate these findings.
    Clinical
    |
    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) • ASXL1 (ASXL Transcriptional Regulator 1)
    |
    FLT3-ITD mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation
    |
    TruSight Myeloid Sequencing Panel
    |
    Onureg (azacitidine oral)
    3ms
    CALCRL knockdown suppresses cancer stemness and chemoresistance in acute myeloid leukemia with FLT3-ITD and DNM3TA-R882 double mutations. (PubMed, Drug Dev Res)
    MOLM13 cells were exposed to stepwise increasing concentrations of cytarabine (Ara-C) to generate MOLM13/Ara-C cells...Furthermore, CALCRL knockdown restricted tumor growth and the chemoresistance of AML in vivo, as well as inducing cell apoptosis in tumor tissues. Together, these data reveal that CALCRL is a vital regulator of leukemia cell survival and resistance to chemotherapy, suggesting CALCRL as a promising therapeutic target for the treatment of FTL3-ITD and DNMT3A-R882 double-mutated AML.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • DNMT3A (DNA methyltransferase 1) • SOX2 • POU5F1 (POU Class 5 Homeobox 1) • NANOG (Nanog Homeobox) • CALCRL (Calcitonin Receptor Like Receptor)
    |
    FLT3-ITD mutation • DNMT3A mutation • DNMT3A R882
    |
    cytarabine
    3ms
    NCI-2018-01789: Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome (clinicaltrials.gov)
    P1/2, N=72, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3)
    |
    TP53 mutation • FLT3-ITD mutation • FLT3 mutation • TP53 deletion
    |
    Venclexta (venetoclax) • Vanflyta (quizartinib) • decitabine
    3ms
    Design and synthesis 1H-Pyrrolo[2,3-b]pyridine derivatives as FLT3 inhibitors for the treatment of Acute myeloid Leukemia. (PubMed, Bioorg Med Chem)
    In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation