rHuman FLt3 Active
- Known as:
- rHuman FLt3 Active
- Catalog number:
- rf00394041-50
- Product Quantity:
- EUR
- Category:
- -
- Supplier:
- Agrenvec
- 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
- Acute myeloid leukaemia (AML) remains associated with poor outcomes in relapsed or refractory disease and in molecularly defined high-risk subgroups. AML with KMT2A rearrangements (KMT2Ar) or NPM1 mutations (NPM1m) shares a dependence on the menin-KMT2A interaction, which sustains HOXA/MEIS1-driven transcription required for leukaemic maintenance. This dependence has provided the rationale for developing menin inhibitors as a targeted approach in selected AML subsets. This review summarises the mechanistic basis, clinical pharmacology, and current clinical role of menin inhibitors in AML. Revumenib, ziftomenib, bleximenib, and enzomenib are orally administered small molecules that disrupt menin-dependent transcription, induce myeloid differentiation, and have shown clinical activity in KMT2Ar and NPM1m AML. Monotherapy has produced clinically relevant remission rates in relapsed or refractory disease, and early-phase combinations with venetoclax-based therapy, hypomethylating agents, intensive chemotherapy, or FLT3 inhibitors have shown higher response rates in selected settings. Despite sharing a common target, these agents differ in dosing schedule, pharmacokinetic profile, CYP3A4-mediated drug-drug interaction potential, sensitivity to food or gastric pH, and safety profile. Differentiation syndrome and QTc prolongation are the principal toxicities requiring monitoring, although QT liability appears to vary across compounds. Acquired resistance-mediated by MEN1 binding-pocket mutations, co-occurring genomic alterations, and adaptive transcriptional or epigenetic programmes-remains a clinical limitation. Current evidence supports menin inhibition as a targeted strategy for molecularly selected AML. Ongoing studies will be important for defining optimal sequencing, combination regimens, approaches to resistance, and the role of pharmacologically informed dose optimisation in routine practice. - Source: PubMed
Publication date: 2026/09/28
Ma ChenchenWang XinWang Jingyi - Leukemia stem cell (LSC) stemness maintenance is a core cause of relapse and therapeutic resistance in acute myeloid leukemia (AML). ANKRD28, an ankyrin repeat domain‑containing gene, has been implicated in malignant phenotypes across various tumors, but its role in regulating AML LSC stemness remains unclear. GEO datasets (GSE9476, GSE30029) and public databases (GEPIA2, TIMER, CCLE) were analyzed to characterize ANKRD28 expression and prognostic relevance in AML and LSCs. ANKRD28 expression in CD34 LSCs from newly diagnosed AML patients was assessed by RT‑qPCR and Western blot. Effects on proliferation, cell cycle, apoptosis, and stemness markers were evaluated using colony formation, CCK‑8, EdU incorporation, flow cytometry, and Western blot. A patient‑derived xenograft (PDX) model was used to assess in vivo tumorigenic capacity. Downstream signaling was explored via GEPIA2 correlation analysis, Western blot, and rescue experiments. Co‑immunoprecipitation (Co‑IP), Rac1 activity assays, and nuclear‑cytoplasmic fractionation were performed to elucidate the underlying mechanism. ANKRD28 was overexpressed in AML tissues, CD34 cells, and CD34⁺‑enriched cell lines, and was associated with FLT3 mutations, relapse, and poor prognosis. Its expression was positively correlated with LSC markers. CD34ANKRD28 cells exhibited greater colony‑forming capacity than CD34ANKRD28 cells. ANKRD28 knockdown inhibited LSC proliferation, induced apoptosis, caused cell cycle arrest, and downregulated stemness markers, whereas overexpression exerted opposite effects. In vivo, ANKRD28 knockdown prolonged survival, reduced LSC infiltration, and alleviated histopathological damage. Mechanistically, ANKRD28 directly bound DOCK180, activated Rac1, promoted STAT3 nuclear translocation and transcriptional activation, and upregulated Myc expression. ANKRD28 is overexpressed in AML CD34 LSCs and sustains stem cell‑like properties via the DOCK180‑Rac1‑STAT3‑Myc axis, serving as a potential therapeutic target for AML. - Source: PubMed
Publication date: 2026/09/28
Zheng XiaoyanDu YueZhang XiaohuiZhu Huachao - Older or medically unfit patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) have poor outcomes with hypomethylating agent (HMA) monotherapy. Venetoclax plus HMA is a modern lower-intensity standard, but FLT3-mutated AML remains biologically heterogeneous, and triplet regimens combining HMA, venetoclax, and a FLT3 inhibitor are increasingly used despite limited randomized comparative evidence. PubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, Scopus, and major hematology/oncology conference proceedings were searched from inception to 12 June 2026 in accordance with PRISMA 2020 and MOOSE guidance. Eligible studies reported primary clinical outcomes for newly diagnosed FLT3-ITD and/or FLT3-TKD AML treated with frontline lower-intensity HMA alone, VEN-HMA doublet, HMA/LIC plus FLT3 inhibitor, or HMA/LIC plus VEN plus FLT3 inhibitor therapy. Comparative effect estimates and single-arm proportions were synthesized only when clinical and statistical assumptions were defensible. Thirteen eligible records were retained. Direct VEN + AZA versus AZA evidence came from one FLT3-mutated pooled subgroup comparison (42 vs. 22 patients), showing CRc 67% versus 36%, RR 1.83 (95% CI 1.01-3.32), and median OS 12.5 versus 8.6 months. The randomized non-venetoclax LACEWING trial showed higher CRc with gilteritinib + AZA than AZA (58.1% vs. 26.5%; HR for OS 0.916; p = 0.753), illustrating that improved remission does not guarantee survival benefit. The principal comparative triplet evidence was one retrospective study: CR/CRi 93% versus 70%, RR 1.32 (95% CI 1.09-1.61), with median OS not reached versus 9.5 months. Prospective and long-term triplet reports described CR/CRi rates of 93%-96%, deep FLT3-ITD MRD negativity, and median OS up to 38.5 months; several reports derive from overlapping institutional series and non-randomized designs, limiting independent corroboration and causal inference. VEN + AZA improves remission compared with AZA in the FLT3-mutated subgroup, but the evidence base is underpowered for FLT3-specific survival conclusions. Triplet therapy produces the strongest remission-depth and MRD signals but has not shown superiority over VEN-HMA in a randomized frontline comparison. On current evidence, triplets are a promising biologically rational strategy requiring direct randomized validation against the contemporary VEN-HMA standard. - Source: PubMed
Shaik Mahboob YounusPatel JayAggarwal VaishaliKakadia SunilDivers Stephen - -mutated acute myeloid leukemia (AML) represents one of the most frequent and biologically distinct AML entities, characterized by the aberrant cytoplasmic localization of the NPM1 mutant protein. The recent advances in molecular biology and translational research have progressively redefined the clinical management of this disease. This narrative review summarizes the evolution of -mutated AML over the last two decades, focusing on the transition from immunohistochemical observations to modern genetics-based and measurable residual disease (MRD)-driven approaches. We discuss the biological role of mutant NPM1, the prognostic impact of co-occurring genetic alterations, and the integration of molecular monitoring into routine clinical practice. Particular attention is given to the prognostic and therapeutic implications of the co-mutational landscape. We also discuss emerging targeted therapies directed against key pathogenic pathways, including the menin-KMT2A axis and nuclear export machinery. Despite significant advances in risk stratification and treatment, considerable heterogeneity in clinical outcomes persists among patients with -mutated AML, indicating that genomic information obtained at diagnosis alone is insufficient to fully capture prognostic differences. Future advances will likely depend on the integration of genetic, transcriptional, and broader cellular-state information to better define biologically relevant disease states and guide more personalized therapeutic strategies. - Source: PubMed
Publication date: 2026/09/19
Cimino GaetanoCaridi MatteoCelenza RosannaMillucci FrancescoCrocioni MartinaSciabolacci SofiaCardinali ValeriaMartelli Maria Paola - Cytarabine is a cornerstone of acute myeloid leukemia (AML) therapy; however, acquired resistance remains a major clinical challenge. FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), a common genetic alteration in AML, is associated with high relapse rates and poor outcomes. Here, we investigated the cellular and molecular mechanisms of acquired cytarabine resistance in FLT3-ITD AML. Cytarabine-resistant MV4-11-CR and MOLM-13-CR cells were generated from parental MV4-11 and MOLM-13 cells, respectively, by stepwise drug selection. Both models exhibited markedly elevated cytarabine IC values and enhanced proliferation. FLT3 expression and activation increased in MV4-11-CR cells but decreased in MOLM-13-CR cells. Midostaurin pretreatment failed to restore cytarabine sensitivity, indicating that altered FLT3 signaling is not a shared mechanism of resistance. Cytogenetic analyses and interphase FISH revealed greater numerical and structural chromosomal heterogeneity in the resistant cells than in their parental counterparts, including the presence of polyploid and near-tetraploid subpopulations. RNA sequencing identified common transcriptional alterations, with among the most significantly downregulated genes. Reduced expression was confirmed at the mRNA and protein levels. knockdown in parental MV4-11 cells attenuated cytarabine-induced cytotoxicity, whereas its re-expression in MV4-11-CR cells partially restored cytarabine sensitivity, supporting the functional contribution of downregulation to acquired resistance. Gene set enrichment analysis demonstrated shared enrichment of G2/M checkpoint and mitotic spindle pathways. Notably, combined TTK/Mps1 and FLT3 inhibition with luvixasertib and midostaurin synergistically suppressed cell viability in both resistant cell lines. These findings identify divergent FLT3 regulation, downregulation, increased chromosomal heterogeneity, and enrichment of mitotic regulatory programs as key features associated with acquired cytarabine resistance. They also support the combined inhibition of TTK/Mps1 and FLT3 as a potential therapeutic strategy for cytarabine-resistant FLT3-ITD AML. - Source: PubMed
Publication date: 2026/09/21
Yen Jui-HungChen Zi-AnLin Yu-XuanJiang Hui-YuLin Liang-InLi Chi-ChengChen Pei-Yi