FLT3 (Fms-related tyrosine kinase 3)

This exploratory study suggests that combining CNAs and gene mutation profiles may potentially improve the existing prognostic evaluation system for NPM1-mutated AML patients. Confirmation of these results requires additional validation in larger prospective cohorts.

These findings establish OSM as a key mediator linking oncogenic STAT5 activation to remodeling of the microenvironment and immune suppression. Targeting OSM signaling therefore represents a promising therapeutic strategy to alleviate disease progression in myeloproliferative neoplasms and related malignancies.

Idarubicin, cytarabine, etoposide (IA ± E) chemotherapy yielded superior survival, while azacitidine+venetoclax (AZA+VEN) regimens underperformed. The study was registered on the Chinese clinical trial registry (ChiCTR) platform (No. ChiCTR2500096484).

In conclusion, FLT3-ITD-based double or triple mutations showed comparable posttransplant outcomes. FLT3-ITD MRD status and early maintenance therapy were key prognostic and therapeutic factors.

This study aims to demonstrate that ABC-14 regimen is non-inferior to "3 + 7" regimen in newly diagnosed AML induction therapy while overcoming AB resistance and reducing toxicity associated with "3 + 7". It seeks to provide a broadly applicable alternative induction strategy for AML.

Patients with DEK-CAN fusion gene positive AML have a very poor prognosis, low primary induced remission rate, and high mortality. For confirmed cases, patients in remission with chemotherapy should undergo allogeneic hematopoietic stem cell transplantation as soon as possible to have a chance of long-term survival.

The 84 patients (63% KMT2Ar, n=53; 23% NPM1c, n=19) who received MENINi were heavily pre-treated: 86% (n=72) had prior intensive chemotherapy (IC), 77% venetoclax (VEN, n=67), and 38% (n=32) allogeneic stem cell transplantation...Of the 60% (n=50) that were treated, common regimens were hypomethylating agent (HMA)/VEN (26%, n=13), clinical trial (26%, n=13), and gilteritinib-based therapy (18%, n=9)...All CR/CRi occurred with HMA/VEN (n=2, 15%), IC+VEN (n=4, 67%), or MENINi switching (bleximenib to revumenib, n=1, 50%)...Outcomes after MENINi failure are poor, but responses occur with VEN-based regimens or MENINi switching. FLT3-ITD, WT1, and MEN1 mutations are associated with resistance.

Post-HCT azacitidine may have a role for MRD-positive AML. In AML with FLT3-internal tandem duplication mutation, post-HCT gilteritinib and sorafenib can be evidence-based strategies to target MRD. In ALL, blinatumomab is a powerful tool to eradicate MRD in patients with Philadelphia (Ph)-positive or Ph-negative ALL; tyrosine kinase inhibitors are indicated for post-HCT management of Ph+ ALL. Despite these advances, the optimal duration and type of intervention still remain unknown for many patients with acute leukemia who have peri-HCT MRD.

Triplet therapies combining hypomethylating agents, venetoclax, and targeted inhibitors are emerging as a promising therapy for older patients with AML unfit for intensive chemotherapy...While effective, the need to remain on indefinite therapy for individuals who are not stem cell transplant candidates and dose optimization/de-escalation strategies remain critical concerns. Herein, we aim to review the current treatment landscape of newly diagnosed and relapsed/refractory FLT3- and IDH1/2-mutated AML and the role of triplet regimens in these molecular subgroups.

Key issues ahead include identifying which genetic features truly affect outcomes, using this information to personalize therapy, predicting who will benefit from targeted drugs, and choosing the best markers to track disease response over time. Looking forward, collaborative efforts are urgently needed to validate pediatric-specific biomarkers, test novel drug combinations, and link genetic data to clinical outcomes to design trials and future treatment strategies.

OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.

Moreover, FTY720 co-treatment resensitized G12D NRAS -mutated M14(R)701 cells to gilteritinib in vivo. Co-treatment inactivated ERK, transcriptionally downregulated SPHK1, and inactivated downstream AKT, p70S6K and BAD, with inactivation abrogated by constitutive SPHK1 expression. The clinically applicable S1PR modulators fingolimod and mocravimod resensitize NRAS -mutated FLT3-ITD AML cells to FLT3 inhibitors, supporting potential clinical efficacy of these combinations.