rHuman FLt3 Active
- Known as:
- rHuman FLt3 Active
- Catalog number:
- RF00394041-50
- Product Quantity:
- 50
- Category:
- -
- Supplier:
- Agren
- Gene target:
- rHuman FLt3 Active
Related genes to: rHuman FLt3 Active
- 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: rHuman FLt3 Active
Related articles to: rHuman FLt3 Active
- NPM1-mutated acute myeloid leukemia (AML) is genetically well-defined, but clinical outcomes remain heterogeneous, suggesting that quantitative clonal features may refine current risk stratification. We analyzed 688 intensively treated NPM1-mutated AML integrating variant allele frequency (VAF), mutation order, and clonal architecture inferred by PyClone and ClonEvol. Co-mutations were present in 97% of patients (median = 3 per case), dominated by DNMT3A (49%), FLT3-ITD (46%), TET2 (22%), and IDH2 (20%). Prognostic modelling of NPM1 VAF identified an optimal cut-off of 31.44%, defining NPM1high and NPM1low groups. NPM1low correlated with splicing-related alterations and independently predicted inferior overall (HR = 1.46; p = 0.037) and relapse-free survival (HR = 1.40; p = 0.036). Gene-specific VAF analyses revealed divergent effects across partners, high DNMT3A, FLT3-OTHER, KRAS, and PTPN11 burdens were adverse, whereas high IDH2 VAF was protective. Combined models showed that patients with NPM1high and favorable co-mutation VAFs had the best outcomes, while dual unfavorable burdens conferred the poorest survival. Mutation ordering inferred from VAFs positioned NPM1 after epigenetic and splicing lesions but before signaling and transcription-factor mutations. Non-canonical orders, such as early FLT3-OTHER/TKD or WT1 prior to NPM1, significantly stratified outcomes. Clonal reconstruction revealed predominantly linear evolutionary trajectories (84.3%), with increased mutational burden and clonal diversity associating with inferior survival. Notably, intra-clonal co-localization of NPM1 with IDH1 or TET2 was associated with improved outcomes, whereas co-localization with WT1 predicted dismal prognosis. These results demonstrate that quantitative and structural dimensions of clonality refine the biological and prognostic landscape of NPM1-mutated AML beyond mutational status alone. - Source: PubMed
Publication date: 2026/06/08
Gil José VicenteSargas ClaudiaAyala RosaGutierrez Norma CPérez-Simón José AntonioGómez-Casares María TeresaLarrayoz María JoséPrados de la Torre EstherCano-Ferri IsabelNavarro IreneGil CristinaBernal Del Castillo TeresaRodríguez-Arbolí EduardoPérez Santaolalla EstherColmenares RafaelTormo MarBergua Burgues Juan MiguelAmigo María-LuzRodríguez-Medina CarlosSerrano JosefinaOliva AnaAlonso-Domínguez Juan ManuelNoriega VíctorAlgarra Jesús-LorenzoOlave Mayte TGarcía Perez Maria JoseCouto María Del CarmenAlmela-Gallego AgataGarcía-Fortes MaríaMadrigal-Toscano Dolores DoloresHermosín LourdesColorado MercedesGarcía-Boyero RaimundoIbañez-Alis FranciscoSolé-Rodríguez MaríaMartinez Chamorro CarmenMateos Maria CGarcía Garay María Del CarmenSolana-Altabella AntonioMartín-Herreros BeatrizMartínez-López JoaquínChillon M CarmenSoria ElenaBilbao-Sieyro CristinaCalasanz Maria J JoséSánchez-García JoaquinBarragan EvaMontesinos Pau - In acute myeloid leukemia (AML), gaining chromosome 8 as the sole abnormality (sole +8) is rare. The prognostic impact and mutation profile of sole +8 AML remain unclear. We retrospectively analyzed a cohort of 75 patients with sole +8 AMLs who were diagnosed and treated at our institution. The genes most frequently harboring mutations in sole +8 AML were ASXL1 (47%), RUNX1 (32%), SRSF2 (32%), TET2 (27%), DNM3A (24%), IDH2 (24%) NRAS (23%), FLT3 (23%), and STAG2 (23%). Age-related differences in the genomic landscape were noted, characterized by a higher frequency of ASXL1, SRSF2, and TET2 mutations in older individuals with sole +8 AML. Sole +8 AML patients had a high frequency of myelodysplasia-related (MR) gene mutations (74.2%). Survival of sole +8 AML patients was inferior compared to European LeukemiaNet (ELN) 2022 intermediate-risk patients (median OS: 14.6 months vs. not reached: NR, p = 0.013), but similar to ELN adverse risk patients (median OS: 16.2, p = 0.72). Categorizing patients on the basis of MR gene mutations revealed that the inferior survival of sole +8 patients may be attributed to the high frequency of MR gene mutations in these patients. These findings indicate the importance of genetic mutations, specifically MR genes, in sole +8 AML. - Source: PubMed
Bahrami Hezaveh EhsanTuringan Mark AnthonyZhou QianghuaWei CuihongTierens AnneSibai HassanChang Hong - Acute myeloid leukemia (AML) remains defined by therapeutic resistance, adverse genetic heterogeneity, and poor long-term survival, underscoring the need for mechanistically informed regimens that exploit core stress-adaptation liabilities. Polo-like kinase 1 (PLK1) is a central regulator of replication recovery and mitotic progression, yet direct PLK1 inhibitors have been limited by tolerability and incomplete target suppression. Here, we define a clinically actionable strategy that functionally targets PLK1 by combining inhibition of the AAA+ ATPase p97/valosin-containing protein (VCP) with the hypomethylating agent decitabine (DAC). Using AML cell lines, primary patient specimens, and an orthotopic in vivo model, we show that the clinically relevant p97 inhibitor CB-5339 induces proteotoxic and replication stress, activates the unfolded protein response, and triggers apoptosis. Formal synergy analyses demonstrate that CB-5339 and DAC cooperate across molecular subtypes, including FLT3-ITD+, KMT2A-rearranged, and TP53-mutant AML, to reduce cell viability at pharmacologically relevant concentrations. Transcriptomic, biochemical, and genetic studies identify synergistic suppression of PLK1 as a central consequence of combination treatment, converting stress-dependent PLK1 reliance into a therapeutic vulnerability. Consistent with this mechanism, PLK1 knockdown phenocopies the antileukemic effects of the combination and enhances sensitivity to both agents. In vivo, CB-5339/DAC is well tolerated, significantly prolongs survival, reduces leukemic burden, and suppresses PLK1 in bone marrow blasts. Together, these data establish p97 inhibition as a rational means to exploit replication and proteotoxic stress in AML and provide strong rationale for clinical evaluation of CB-5339 plus DAC in high-risk disease. - Source: PubMed
Publication date: 2026/06/05
Nawrocki Steffan TWang NingEspitia Claudia MWu HarleyVilla Celi ClaudiaOlea JulianZarand PanizDadrastoussi HomaMatta HittuSureshkumar SruthiGamble Madison EHakim Natalie LDrum DavidAngeles JackWu KaijinZhong Jiang FChen XuelianDuong AlexCarew Jennifer SKelly Kevin R - Quizartinib is an oral, potent, selective FMS-like tyrosine kinase 3 (FLT3) inhibitor, approved for the treatment of FLT3-internal tandem duplication (ITD)-positive acute myeloid leukemia (AML) and under investigation in patients with newly diagnosed FLT3-ITD-negative AML. Quizartinib is metabolized by cytochrome P450 3A (CYP3A) in vitro, primarily into the active metabolite AC886, a CYP3A substrate. These phase 1, open-label, randomized, parallel-group trials assessed the effect of efavirenz, a moderate CYP3A inducer, and rufinamide, a weak CYP3A inducer, on the pharmacokinetics of quizartinib and AC886, and the safety and tolerability of quizartinib in healthy participants. Each study enrolled 32 participants; 16 received 60 mg quizartinib alone and 16 received 60 mg quizartinib plus either 600 mg efavirenz or 400 mg rufinamide. Coadministration with efavirenz decreased the maximum plasma concentration (C) and area under the plasma concentration-time curve extrapolated to infinity (AUC) of quizartinib by ~45% and ~90%, respectively, versus quizartinib alone; AC886 C and AUC also decreased by ~68% and ~96%, respectively. Coadministration with rufinamide had modest impact on quizartinib exposure (C and AUC decreased by ~19% and ~34%, respectively, vs. quizartinib alone). Coadministration of rufinamide and quizartinib decreased AC886 C and AUC by ~47% and ~53%, respectively, versus quizartinib alone. Quizartinib was well tolerated and no new safety signals were observed. These results suggest that concomitant use of quizartinib and moderate CYP3A inducers should be avoided. Concomitant use of weak CYP3A inducers does not warrant dose adjustment, since the impact on quizartinib exposure is clinically nonrelevant. - Source: PubMed
Yoo YoungJunZahir HamimInaba ShinichiKoo KyoinGarimella TusharAbutarif MalazZheng MingKamiyama EmiXu Yuan - Wild-type (WT) gastrointestinal stromal tumors (GISTs) are a rare and molecularly heterogeneous subset of GISTs lacking and mutations. These tumors pose significant diagnostic and therapeutic challenges due to resistance to standard tyrosine kinase inhibitors and a wide spectrum of genetic drivers. - Source: PubMed
Publication date: 2026/06/05
Xue ShuangLi ChunxiaoLi MeiFu FangfangZhang GuangtanLu ChangLiu Qiuyu