FLT3 (Fms-related tyrosine kinase 3)

In this review, we will describe the current status of CAR T/NK cell development for AML. We will also introduce a new CAR T-cell or NK-cell therapy that targets mismatched HLA-DRB1 in patients with AML who have relapsed following an allogeneic haematopoietic stem cell transplant.

Our findings indicate that while relapse after allo-HCT in AML is genetically diverse, timing of recurrence remains the most critical determinant of outcome. Given that certain genetic changes may inform therapeutic options, these findings highlight the relevance of longitudinal molecular monitoring especially during the early post-transplant period.

In vivo, FLC-8 inhibited MV4-11 xenograft growth (TGI: 136-178% at 10-50 mg/kg) without overt toxicity. These findings identify Cys807 as a covalent binding hotspot in FLT3 and establish FLC-8 as a promising scaffold for next-generation FLT3 inhibitor development.

Molecular docking further supported these findings, showing favorable binding energy (-7.98 kcal/mol) compared to regorafenib (-7.13 kcal/mol). Collectively, these results highlight PL-13 as a promising lead compound for further optimization toward CRC therapy.

We critically evaluate the preclinical and clinical development of menin inhibitors, including revumenib, ziftomenib, bleximinib, and icovamenib, summarizing efficacy signals in relapsed/refractory disease, safety profiles, and emerging resistance mechanisms. Special attention is given to combination strategies with venetoclax, FLT3 inhibitors, chemotherapy, and epigenetic agents, which aim to enhance response durability and mitigate resistance. Finally, we discuss ongoing clinical trials, unresolved challenges in patient selection and sequencing, and future directions for integrating menin inhibition into precision-based treatment paradigms for acute leukemia.

P2, N=35, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Since the IPSS-R and IPSS-M showed a poorly prognostic separation for MDS/AML patients, we further established a new prognostic model MDS/AML-IPSS-M and significantly improved its prognostic discrimination ability. Taking together, our research findings enhance the understanding of the molecular biology of MDS and can provide important guidance for the clinical identification of MDS/AML patients that might benefit clinical decision-making and therapeutic research.

Measurable residual disease (MRD) assessment using multiparameter flow cytometry and molecular assays is increasingly used to refine post-remission decisions, including transplantation and maintenance strategies, but is constrained by assay variability, clonal hematopoiesis, and limited evidence for MRD-directed interventions. This narrative review synthesizes the evolving genomic landscape, guideline-endorsed targeted therapies, and investigational strategies in AML, and provides a practical framework that integrates genomic profiling, MRD-informed decision-making, and algorithmic treatment pathways while highlighting real-world barriers to implementation and equity.

Moreover, F-17 showed potent selectivity and inhibition activity for FLT3-mutated cells both in vitro and in vivo. Collectively, the work provided a new insight for FLT3 inhibitor development.

Mechanistically, KD rewired anabolism toward fatty acid oxidation and glycine-utilizing pathways, modulated the expression of FLT3 signaling pathways and lipid biosynthesis, and promoted tumor cell differentiation. In conclusion, this study shows that KD reduces FLT3i resistance, offering a promising therapeutic solution.