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    GENE:

    FLT3 (Fms-related tyrosine kinase 3)

    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
    13h
    Constitutive Flt3 signaling impacts conventional dendritic cell function. (PubMed, Immunol Cell Biol)
    Cytokine secretion patterns, antigen uptake, antigen proteolysis and antigen presenting function differed between WT and Flt3ITD/ITD subsets, particularly cDC2. In summary, Flt3 signaling impacts the function of terminally differentiated cDCs with important consequences for antigen presentation.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • CD8 (cluster of differentiation 8) • ITGAM (Integrin, alpha M) • ITGAE (Integrin Subunit Alpha E) • CDK1 (Cyclin-dependent kinase 1) • ITGAX (Integrin Subunit Alpha X) • CD86 (CD86 Molecule)
    19h
    A systematic review of second-generation FLT3 inhibitors for treatment of patients with relapsed/refractory acute myeloid leukemia. (PubMed, Leuk Res)
    These targeted therapies offer promise for managing this subgroup of AML patients, but further research is needed to optimize their use. This study underscores the importance of personalized treatment based on genetic mutations in AML, paving the way for more effective and tailored approaches to combat the disease.
    Review • Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
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    Venclexta (venetoclax) • Xospata (gilteritinib) • Vanflyta (quizartinib)
    1d
    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
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    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • WT1 (WT1 Transcription Factor)
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    FLT3-ITD mutation • NPM1 mutation
    2d
    Genetic mutations and immune microenvironment: unveiling the connection to AML prognosis. (PubMed, Hematology)
    The distribution of NK cells show significant differences among AML patients in different survival periods. This results implies that distinct genetic mutations may play a role not only in tumor initiation but also in shaping the tumor microenvironment, consequently impacting prognosis.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    6d
    Precision off-the-shelf natural killer cell therapies for oncology with logic-gated gene circuits. (PubMed, Cell Rep)
    The NOT gate protects healthy hematopoietic stem cells (HSCs) using an inhibitory CAR targeting endomucin, a protective antigen unique to healthy HSCs. NK cells with the combined OR-NOT gene circuit kill multiple AML subtypes and protect primary HSCs, and the circuit also works in vivo.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • CD33 (CD33 Molecule)
    6d
    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
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    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)
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    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation
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    Venclexta (venetoclax) • S63845 • emavusertib (CA-4948) • zelavespib intravenous (PU-H71 IV)
    7d
    Clinical outcomes and treatment patterns in adults with FLT3-ITDmut+ acute myeloid leukemia undergoing allogeneic hemopoietic cell transplantation in the US and Canada. (PubMed, Transplant Cell Ther)
    In this largest study to date of patients from the US and Canada with FLT3-ITDmut+ AML, disease status of CR1 at the time of alloHCT was associated with better clinical outcomes. Additional factors were identified that may also impact clinical outcomes, and in total, have the potential to inform clinical decision-making.
    Clinical data • Journal
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    FLT3 (Fms-related tyrosine kinase 3)
    7d
    Advancements and Challenges in the Treatment of AML. (PubMed, Am Soc Clin Oncol Educ Book)
    FLT3 inhibitors, gemtuzumab ozogamicin, and CPX-351 have been shown to improve outcomes for specific subsets of patients. Venetoclax (VEN) with a hypomethylating agent (HMA) is the standard-of-care frontline regimen for most older patients, except perhaps for those with an IDH1 mutation where ivosidenib with azacitidine may also be considered...This article focuses on recent updates and ongoing challenges in the management of AML, with a particular focus on the ongoing challenge of secondary AML and considerations regarding the selection of initial therapy in younger patients. An overview of common side effects and toxicities associated with targeted therapies is also presented here, along with recommended strategies to mitigate these risks.
    Review • Journal
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    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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    IDH1 mutation
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    Venclexta (venetoclax) • azacitidine • Tibsovo (ivosidenib) • Mylotarg (gemtuzumab ozogamicin) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
    7d
    Gene Profile and Clinical Significance of Concomitant Mutations in CN-AML Patients with CEBPA Mutation (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    CN-AML patients with CEBPA mutation have specific concomitant gene profile, and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.
    Retrospective data • Journal
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    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • TET2 (Tet Methylcytosine Dioxygenase 2) • WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • GATA2 (GATA Binding Protein 2)
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    CEBPA mutation
    7d
    Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with GATA2 Gene Mutation (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification, and it is significantly associated with CEBPAdm and NRAS co-mutations. The prognostic significance of GATA2 is influenced by CEBPAdm. The choice of "3+7" or "DCAG" induction regimen in patients with GATA2 mutation does not affect their CR rate, while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.
    Retrospective data • Journal
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    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • WT1 (WT1 Transcription Factor) • GATA2 (GATA Binding Protein 2)
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    NRAS mutation • GATA2 mutation
    7d
    Correlation of miR-155 Expression with Drug Sensitivity of FLT3-ITD+ Acute Myeloid Leukemia Cell Line and Its Mechanism (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    Drug sensitivity of MV411 cells to doxorubicin, quizartinib and midostaurin can be enhanced significantly after miR-155 knockout, which is related to the inhibition of multiple signaling pathways including mTOR and Wnt signaling pathways.
    Preclinical • Journal
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    FLT3 (Fms-related tyrosine kinase 3) • MIR155 (MicroRNA 155)
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    miR-155 expression
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    doxorubicin hydrochloride • Rydapt (midostaurin) • Vanflyta (quizartinib)
    8d
    A Study of Gilteritinib (ASP2215) Combined With Chemotherapy in Children, Adolescents and Young Adults With FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov)
    P1/2, N=97, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Sep 2026 --> Jul 2031 | Trial primary completion date: Nov 2024 --> Aug 2027
    Trial completion date • Trial primary completion date
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    FLT3 (Fms-related tyrosine kinase 3)
    |
    cytarabine • Xospata (gilteritinib) • fludarabine IV
    8d
    RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives. (PubMed, Blood Cancer J)
    Recent evidence also indicates that RAS mutations drive resistance to targeted therapies, particularly FLT3, IDH1/2, or JAK2 inhibitors, as well as the venetoclax-azacitidine combination. The success of direct RAS inhibitors in patients with solid tumors has brought renewed optimism that this progress will be translated to patients with hematologic malignancies. In this review, we highlight key insights on RAS mutations across myeloid malignancies from the past decade, including their prevalence and distribution, cooperative genetic events, clonal architecture and dynamics, prognostic implications, and therapeutic targeting.
    Review • Journal
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    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • RAS (Rat Sarcoma Virus)
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    RAS mutation
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    Venclexta (venetoclax) • azacitidine
    8d
    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
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    FLT3 (Fms-related tyrosine kinase 3) • CD33 (CD33 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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    FLT3-ITD mutation
    8d
    Revisiting the role of measurable residual disease in FLT3 mutated acute myelogenous leukemia. (PubMed, Expert Rev Hematol)
    No abstract available
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
    8d
    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
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    FLT3 (Fms-related tyrosine kinase 3) • CDK6 (Cyclin-dependent kinase 6) • CSF1R (Colony stimulating factor 1 receptor)
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    FLT3-ITD mutation • FLT3 mutation • FLT3 wild-type
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    narazaciclib (HX301)
    9d
    SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression. (PubMed, EMBO J)
    Importantly, succinyl-CoA level and POLRMT succinylation are downregulated in FLT3-mutated clinical leukemia samples, linking enhanced mitobiogenesis to cancer progression. Together, SUCLG1 connects succinyl-CoA with POLRMT succinylation to modulate mitochondrial function and cancer development.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
    10d
    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)
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    FLT3-ITD mutation • FLT3 mutation
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    Vanflyta (quizartinib)
    10d
    Extramedullary infiltration in pediatric acute myeloid leukemia: Results from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. (PubMed, Pediatr Blood Cancer)
    EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
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    Mylotarg (gemtuzumab ozogamicin)
    10d
    KB-LANRA- 1001: A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov)
    P1/2, N=24, Terminated, Kronos Bio | Trial completion date: Oct 2024 --> Apr 2024 | Active, not recruiting --> Terminated; Sponsor decision
    Trial completion date • Trial termination • Combination therapy
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
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    Xospata (gilteritinib) • lanraplenib (GS-9876)
    12d
    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
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    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
    13d
    Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1. (PubMed, iScience)
    However, cytokine-mediated drug resistance can be overcome by a pan-RAS inhibitor. We show that cytokines instruct AML growth via the transcriptional regulators AP-1 and RUNX1 and that pan-RAS drugs bypass this barrier.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1)
    14d
    High remission rates and transition to allogeneic transplant in older patients with newly diagnosed FLT-3 mutated acute myelogenous leukemia with midostaurin plus intensive chemotherapy. (PubMed, Leuk Lymphoma)
    No abstract available
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
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    Rydapt (midostaurin)
    15d
    Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. (PubMed, Curr Hematol Malig Rep)
    Lower-risk MDS (LR-MDS) treatment ranges from observation to supportive measures and erythropoiesis-stimulating agents (ESAs), with emerging therapies like luspatercept showing promise...Emerging treatments, including oral HMAs and novel agents targeting FLT3, and IDH 1/2 mutations, show promise. Future research should refine treatment strategies for this elderly population focusing on quality-of-life improvement.
    Review • Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    Reblozyl (luspatercept-aamt)
    15d
    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
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    FLT3 (Fms-related tyrosine kinase 3) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • GLI2 (GLI Family Zinc Finger 2)
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    FLT3-ITD mutation • FLT3 mutation
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    daunorubicin • arsenic trioxide
    18d
    A practical algorithm for acute myeloid leukaemia diagnosis following the updated 2022 classifications. (PubMed, Crit Rev Oncol Hematol)
    We propose a practical algorithm for the speedy diagnosis of AML. Future classifications may need to incorporate gene mutation combinations to enable personalised treatment regimens in the management of patients with AML.
    Review • Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
    19d
    FLAG/FLAG-Ida Regimen in Secondary and Relapsed/Refractory Acute Myeloid Leukemia-Even in the Era of New Treatment Modalities Still a Significant Player. (PubMed, J Clin Med)
    The aim of the study was to assess the efficacy and toxicity of fludarabine, cytarabine, and granulocyte-colony stimulation factor (FLAG) with or without idarubicin (-Ida) and to discuss novel therapies in this setting. Among the variables, including age, FLT3 mutation status, European LeukemiaNet (ELN) 2022 classification risk, FLAG vs. FLAG-Ida, and aHSCT, a multivariate analysis revealed that only aHSCT significantly influenced overall survival. (4) FLAG(-Ida) chemotherapy remains an effective salvage chemotherapy for patients with r/r and secondary AML with a plan of proceeding to aHSCT.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
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    cytarabine • idarubicin hydrochloride • fludarabine IV
    21d
    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
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    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
    21d
    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
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    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
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    cytarabine • decitabine • aclarubicin
    21d
    FLT-3 mutation maybe an inferior predictor of daratumumab therapy in acute myeloid leukemia patients relapsed after allogeneic stem cell transplantation. (PubMed, Int J Lab Hematol)
    No abstract available
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
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    Darzalex (daratumumab)
    22d
    Alpha/Beta T Cell and CD19+ B Cell Depletion in Allogeneic Stem Cell Transplantation in Patients With Malignant Diseases (clinicaltrials.gov)
    P2, N=20, Recruiting, University of Florida | Not yet recruiting --> Recruiting
    Enrollment open
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    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation • CBL mutation • Chr t(9;11)
    22d
    Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia. (PubMed, Leukemia)
    The emergence of these novel agents in AML offers patients a new modality of therapy, and shifts treatment paradigms toward individualized medicine. In this review, we outline the role of IDH mutations in malignant transformation, focus in on a novel group of targeted therapeutic agents directed toward IDH1- and IDH2-mutant AML, and explore their impact on prognosis in patients with AML.
    Review • Journal
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    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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    IDH2 mutation • FLT3 mutation
    23d
    Gemtuzumab ozogamicin plus midostaurin in combination with standard '7 + 3' induction therapy in newly diagnosed AML: Results from the SAL-MODULE phase I study. (PubMed, Br J Haematol)
    Three dose levels of midostaurin and one to three sequential doses of 3 mg/m2 GO in combination with '7 + 3' induction were evaluated. Based on safety findings in 12 patients, our results show that 3 mg/m2 GO on Days 1 + 4 and 100 mg midostaurin on Days 8-21 can be safely combined with IC in newly diagnosed AML.
    P1 data • Journal • Combination therapy
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    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation
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    Rydapt (midostaurin) • Mylotarg (gemtuzumab ozogamicin)
    24d
    Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025
    Trial completion date • Trial primary completion date
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • BCOR mutation • Chr del(5q) • STAG2 mutation • FLT3 wild-type • Chr t(9;11) • ZRSR2 mutation
    |
    cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)
    24d
    NKX101-101: NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS (clinicaltrials.gov)
    P1, N=61, Active, not recruiting, Nkarta Inc. | Recruiting --> Active, not recruiting | N=90 --> 61
    Enrollment closed • Enrollment change
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    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation
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    cytarabine • cyclophosphamide • decitabine • fludarabine IV • NKX101
    24d
    Innovations in conditioning and post-transplant maintenance in AML: genomically informed revelations on the graft-versus-leukemia effect. (PubMed, Front Immunol)
    There is an urgent need to better understand how these emerging therapies modulate the two sides of the GVHD vs. GVL coin: 1) how molecularly or immunologically targeted therapies affect engraftment, GVHD potential, and function of the donor graft and 2) how these therapies affect the immunogenicity and sensitivity of leukemic clones to the GVL effect. By maximizing the synergistic action of molecularly targeted agents, immunomodulating agents, conventional chemotherapy, and the GVL effect, there is hope for improving outcomes for patients with this often-devastating disease.
    Review • Journal • Post-transplantation
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    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    24d
    Fulminant Clostridioides difficile infection during treatment with FLT3 inhibitor for acute myeloid leukemia (PubMed, Rinsho Ketsueki)
    An 80-year-old man with FLT3-TKD mutation-positive acute myeloid leukemia (AML) relapsed during consolidation therapy with venetoclax/azacitidine and was started on gilteritinib as salvage therapy. The patient was discharged from the intensive care unit on the 18th day after the onset of CDI. We report this case not only due to the rarity of fulminant CDI during AML treatment, but also because it is a valuable example of effective treatment of fulminant CDI with fidaxomicin.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3-TKD mutation
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    Venclexta (venetoclax) • Xospata (gilteritinib) • azacitidine
    26d
    The RAS-signaling-pathway-mutation-related prognosis in B-cell acute lymphoblastic leukemia: A report from South China children's leukemia group. (PubMed, Hematol Oncol)
    Four cases relapsed in the lately 3 years were RAS signaling pathway mutation-positive. RAS signaling pathway mutation is an important biomarker for poorer relapse-free survival in pediatric B-ALL patients despite good early MRD levels.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CREBBP (CREB binding protein)
    |
    NRAS mutation • RAS mutation • CREBBP mutation
    26d
    Causes and risk factors for early death in adult patients with acute promyelocytic leukemia: a real-life experience. (PubMed, Hematol Transfus Cell Ther)
    ED remains a substantial challenge in APL, especially in real-world settings with hemorrhage and infection being the leading causes. ECOG status and WBC count emerged as independent risk factors, while age and platelet count lacked a 30-day prognostic correlation. Evaluating prognostic enhancement tools in controlled trials and real-life settings is pivotal to improving APL outcomes.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation
    26d
    Unveiling the signaling network of FLT3-ITD AML improves drug sensitivity prediction. (PubMed, Elife)
    Interestingly, our analysis reveals that the JNK kinase pathway plays a crucial role in the tyrosine kinase inhibitor response of FLT3-ITD cells through cell cycle regulation. Finally, our work shows that patient-specific logic models have the potential to inform precision medicine approaches.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3)
    26d
    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)
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    FLT3-ITD mutation • FLT3 mutation • DNMT3A mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation
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    Venclexta (venetoclax) • cytarabine • Xospata (gilteritinib) • decitabine • aclarubicin
    27d
    Day-21 bone marrow findings incorrectly designate residual leukaemia in FLT3-mutated acute myeloid leukaemia treated with intensive induction plus midostaurin: a morphology-focused study. (PubMed, Pathology)
    In summary, based on morphology alone, D21-BM assessment following 7+3 intensive induction plus midostaurin for FLT3-AML incorrectly designates RL in some patients; thus correlating with associated flow and molecular results is essential before concluding RL following first induction. Where remission status is unclear, repeat D28-BMs should be performed.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3)
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    FLT3 mutation
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    Rydapt (midostaurin)