FLT3 (Fms-related tyrosine kinase 3)

The representative compound 6s demonstrates superior dual-targeting properties, exhibiting 150-fold higher FLT3 inhibition (half-maximal inhibitory concentration (IC50) = 14 nM) compared with the reference drug tandutinib (IC50 = 2098 nM) and 2.9-fold higher HDAC1 inhibition (IC50 = 27 nM) relative to vorinostat (SAHA; IC50 = 79 nM). Importantly, in the Jeko-1 xenograft model, 6s achieves 53.34 % tumor growth inhibition at a dose of 30 mg/kg with no observable toxicity. Collectively, these results indicate that 6s is a potent dual FLT3/HDAC inhibitor with promising therapeutic potential for hematologic malignancies.

Overall, dapolsertib demonstrated modest single-agent activity in patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT03008187.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.

Insertion sites located in Hinge Region(HR)/β1 domain and juxtamembrane domain (JMD) derived significantly greater benefit from early FLT3 inhibitor therapy(primarily sorafenib), showing significantly prolonged overall survival...In the era of FLT3-ITD targeted drug therapy combined with transplantation, the insertion site of FLT3-ITD based on high throughput sequencing results helps predict the efficacy of FLT3 inhibitors. Integrating white blood cell count with HR/β1 insertion site can identify a high-risk patient subgroup likely to benefit from FLT3 inhibitor therapy.

Our results lend support to the presumption that inflammatory cytokines are important biomarkers that associate with DR severity and may represent novel targets for inhibition. The authors have no proprietary or commercial interest in any materials discussed in this article.

The case highlights the importance of distinguishing de novo lymphoid malignancies from MLN-eo-TK, especially when JAK2 rearrangements are detected. Recognition of the clonal myeloid component during or after lymphoid-directed therapy has important diagnostic and therapeutic implications, supporting the use of targeted JAK2 inhibition in addition to standard chemotherapy.

P2, N=147, Recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> May 2029 | Trial primary completion date: Oct 2025 --> May 2029

P1/2, N=73, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

P1/2, N=42, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

This case adds to the limited literature reporting cup-like nuclear morphology in B-ALL, which is typically associated with varied cytogenetic abnormalities, including BCR::ABL1 fusion and hyperdiploidy [3, 4]. The findings emphasize the critical role of FCI and molecular studies in distinguishing AML from B-ALL or mixed phenotype acute leukemias.

No new safety concerns were identified. Long-term gilteritinib treatment improved clinical outcomes compared with SC and was well-tolerated in a predominantly Asian population with relapsed/refractory FLT3-mutated AML.

After oral administration, the SEDDS formulation increased the ZZP-2 plasma area under the curve (AUC0-∞) by 3.7-fold relative to a suspension formulation in Sprague-Dawley (SD) rats and significantly prolonged survival in MOLM-13-luciferase-bearing NSG mice compared to positive controls sunitinib and gilteritinib, without noticeable toxicity. Our study presents a novel FLT3-ITD inhibitor with high potency and in vivo stability.