Ask about this productRelated genes to: CD135 antibody
- Gene:
- FLT3 NIH gene
- Name:
- fms related tyrosine kinase 3
- Previous symbol:
- -
- Synonyms:
- STK1, FLK2, CD135
- Chromosome:
- 13q12.2
- Locus Type:
- gene with protein product
- Date approved:
- 1990-07-30
- Date modifiied:
- 2019-04-23
Related products to: CD135 antibody
Related articles to: CD135 antibody
- DNA topoisomerase II-binding protein 1 (TopBP1) plays a critical role in V(D)J recombination and DNA damage repair during B and T cell development. However, its role in the development of conventional dendritic cells (cDCs) remains unexplored. Mice with DC-specific depletion of TopBP1 (TopBP1) exhibited accelerated tumor progression due to impaired anti-tumor immunity, which was characterized by cDC deficiency and pre-DC accumulation. The cDC deficiency observed in TopBP1 mice was not attributable to cell death resulting from accumulated DNA damage during DC development. Notably, Flt3 ligand (Flt3L)-mediated tumor immunotherapy was ineffective in TopBP1 tumor-bearing mice. Here we demonstrate that TopBP1 is required not only for the steady-state differentiation of total cDCs, including both cDC1 and cDC2, but also for the terminal differentiation of XCR1CD24⁺ emergency progenitors (CD11c⁺cKit⁺) into XCR1⁺CD24⁺ cDC1s in response to Flt3L. Furthermore, TopBP1 was found to be essential for the function of the PU.1-IRF8 heterodimeric transcription factor complex, which is critical for cDC lineage specification. TopBP1 directly binds to this complex and facilitates the transcription of downstream target genes required for cDC development. These findings establish TopBP1 as a pivotal regulator of both steady-state and Flt3L-driven emergency cDC differentiation, particularly in guiding emergency progenitors into functional cDC1s. Our study highlights the previously unrecognized role of TopBP1 as a co-regulator of lineage-defining transcription factors and as a determinant of Flt3L-mediated anti-tumor efficacy. - Source: PubMed
Publication date: 2026/05/08
Cha Min-SukKang Myeong-HoLee JinjooHong JungHyubJeong Yu SunBae Yoe-SikLee HoPark Seok-HeeBae Yong-Soo - Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are among the most clinically relevant molecular abnormalities in acute myeloid leukemia (AML); however, the therapeutic significance of rare non-canonical FLT3 mutations involving the juxtamembrane domain (JMD) remains poorly defined. We report a 34-year-old woman with acute monocytic leukemia harboring a rare FLT3-JMD missense mutation (V579A) who experienced early relapse following standard induction and consolidation chemotherapy. Targeted next-generation sequencing revealed the presence of FLT3 V579A along with a concurrent truncating ARID1A mutation. Salvage therapy with the type I FLT3 inhibitor gilteritinib induced rapid hematologic remission within three weeks, allowing successful bridging to haploidentical allogeneic hematopoietic stem cell transplantation. Three months after transplantation, the patient relapsed, and genomic analysis demonstrated loss of the FLT3-mutated clone with the emergence and expansion of TP53-mutated independent clones, indicating clonal evolution and an apparent shift away from FLT3-dependent disease biology. This case suggests that AML harboring rare FLT3-JMD point mutations may exhibit transient dependence on FLT3 signaling and may respond to FLT3 inhibition despite the absence of canonical FLT3 alterations. These findings highlight the potential value of extended molecular profiling and longitudinal genomic assessment to identify potential therapeutic targets and mechanisms of resistance in relapsed AML. - Source: PubMed
Publication date: 2026/05/09
Nakao FumihikoShima TakahiroTakigawa KenSemba YuichiroJinnouchi FumiakiYamauchi TakujiOdawara JunKikushige YoshikaneMori YasuoKato KojiMaeda TakahiroAkashi Koichi - Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) occurs in ~15% of pediatric patients with acute myeloid leukemia (AML) and is associated with high relapse risk with conventional chemotherapy. Gilteritinib is a selective, next-generation FLT3 inhibitor (FLT3i) approved for adults with relapsed/refractory FLT3‑mutated AML, but pediatric-specific data remain limited. The multi-national phase 1/2 SKIPPER study evaluated gilteritinib combined with fludarabine and cytarabine chemotherapy and granulocyte colony‑stimulating factor (FLAG) in children and adolescents/young adults with relapsed/refractory FLT3‑ITD AML. Nine patients, aged 8-15 years, were enrolled in phase 1 of the study between 2020 and 2023. Recruitment challenges, including disease rarity, off‑label FLT3i availability, and competing trials, led to study termination after phase 1. The composite complete remission rate in the study population was 66.7% (95% confidence interval: 29.9%-92.5%). Two‑year event‑free and overall survival probability was 41.7% and 55.6%, respectively. Treatment‑emergent adverse events, most commonly reversible hepatic enzyme elevations and cytopenias, were consistent with known toxicity profiles of gilteritinib and FLAG. Pharmacokinetic parameters were comparable to those of adults, and pharmacodynamic plasma inhibitory activity assays confirmed sustained FLT3 inhibition. No dose‑limiting toxicities were observed, and the recommended phase 2 dose of gilteritinib was established at 2 mg/kg/day for patients ≥2 years old. The gilteritinib and FLAG regimen had manageable safety, induced high remission rates, and enabled allogeneic hematopoietic stem cell transplant for several patients. Although limited by a small sample size, these findings support further evaluation of gilteritinib in pediatric patients with FLT3-mutated AML, particularly in frontline settings (ClinicalTrials.gov Identifier: NCT04240002). - Source: PubMed
Publication date: 2026/05/08
Connor PhilipRibeiro Raul CCatala AlbertNorton AliceSchündeln Michael MHasabou NahlaDelgado DavidHeinloth Alexandra NatalieHill Jason EGill Stanley CBigirumurame TheophileTasian Sarah KLocatelli Franco - Acute myeloid leukemia (AML) is a heterogeneous malignancy with a poor prognosis. Genetic and molecular profiling help guide treatment decisions, including the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT), to reduce relapse risk. This study evaluated the impact of individual and co-mutational genetic profiles in AML patients in first complete remission after receiving allo-HSCT using data from the PETHEMA registry. A retrospective analysis assessed overall survival and relapse-free survival (RFS). Cox regression identified significant variables used to develop a risk score based on hazard ratios, incorporating age, AML type, transplant timing, and genetic/molecular alterations. A total of 717 patients (median age 56.5 years) were included, most classified as adverse risk by ELN2022 criteria. Both ELN2017 and ELN2022 risk classifications were validated. Multivariate analysis showed that DNMT3A, SF3B1, TP53, and WT1 mutations were linked to shorter RFS, whereas FLT3-ITD mutations correlated with prolonged RFS. These findings were integrated into a proposed prognostic score, which was validated. Therefore, this study highlights the prognostic importance of genetic mutations in AML patients undergoing allo-HSCT. These insights could inform pre-transplant strategies, including donor selection and conditioning regimens, as well as post-transplant maintenance therapy. - Source: PubMed
Publication date: 2026/05/07
Colmenares RafaelBarragán EvaRodríguez-Veiga RebecaTorres-Miñana LauraSánchez-García JoaquínTormo MarBernal TeresaMartínez-Sánchez PilarRodríguez-Arbolí EduardoGil CristinaSoria-Saldise ElenaSerrano JosefinaColorado MercedesGarcía-Fortes MaríaBilbao CristinaLópez-Lorenzo José LuisLarráyoz María JoséPérez-Santaolalla EstherLavilla-Rubira EsperanzaAlgarra LorenzoGarcía-Garay María CarmenChillón CarmenTorres-Ochando MelissaCouto CarmenGarcía-Boyero RaimundoAlmela ÁgataNoriega VíctorCallejas MartaBarrios ManuelCasado SoledadBalerdi AmaiaCabello AnaLabrador JorgeMateos María CarmenAmigo María LuzPérez-Encinas ManuelGarcía-Pérez María JoséCostilla LissetteBergua JuanCarreño-Tarragona GonzaloMartínez-López JoaquínAyala RosaMontesinos Pau - - Source: PubMed
Publication date: 2026/05/07
Crupi FrancescaCiolli GaiaPiccini MatteoScappini BarbaraFasano LauraQuinti ElisaPasquini AndreaCaroprese JessicaGianfaldoni GiacomoMotta GiovannaSanti RaffaellaMaccari ChiaraGuglielmelli PaolaVannucchi Alessandro MMannelli Francesco