FLT3 (Fms-related tyrosine kinase 3)

This is the first multi-center study conducted in Mexico among patients with FLT3+ R/R AML. Despite high remission rates following 1 L induction therapy, patients experienced disease progression and HRU remained high, indicating an unmet need. Future studies are warranted to assess how outcomes evolve with novel treatments.

These findings demonstrated associations between genetic alterations and clinical features, disease progression, and prognosis in Chinese patients with myeloid malignancies. However, the prognostic associations should be interpreted cautiously, as none of the evaluated variables remained independent prognostic factors in multivariate models.

The n-2023 CN resolves uncertainty in genetic risk stratification for Chinese AML patients. The novel multi-omics model incorporates immunophenomics and clinical and cytogenetic factors, captures comprehensive AML characteristics, enhances prognostic precision, and provides reliable guidance for personalized treatment, including HSCT selection.

Glutamine deprivation or telaglenastat treatment abrogated c-CBL upregulation in hypoxia and preserved FLT3-ITD and p-STAT5 expression and FLT3 inhibitor sensitivity. Telaglenastat synergized with FLT3 inhibitors in hypoxia, supporting clinical testing.

Deep sequencing of FLT3-ITD is a highly sensitive method for MRD monitoring in children with AML, with significant potential for assessing treatment response and detecting imminent relapse at an early stage. It may serve as a valuable molecular MRD method, especially as a complement to flow cytometry.

Our results confirm intracellular inhibition of TAK1 by several FLT3 inhibitors in clinical use. Given that FLT3 inhibitors are administered chronically to treat AML, the nonharmful unintended off target inhibition of TAK1 in vivo by current FLT3 inhibitors provides some insight into the safety and tolerability of chronic TAK1 inhibition in patients.

We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and proliferation factors to effectively block leukemogenesis. This work identifies potential clinical utility of a targeted, triplet combination therapy for treatment of AML.

In patients with newly diagnosed FLT3-ITD-negative AML achieving CRc1, quizartinib improved OS and DFS in the overall population. Notably, the clinical benefit of quizartinib was observed regardless of allo-HCT, and appeared more evident in patients who did not proceed to transplant.

Overall, this study demonstrates that a significant proportion of CN-AML cases harbor clinically relevant SVs, especially those associated with adverse prognosis, that escape detection by standard techniques. Our results support the use of OGM as a streamlined, genome-wide tool for both research and diagnostic applications in AML.

APL may exhibit immunophenotypic aberrancies mimicking MPAL. Molecular confirmation of PML::RARA and an integrated diagnostic approach are essential to avoid misclassification and ensure timely therapy.

These results establish TREM1 as a biomarker of high-risk AML characterized by FLT3/CD123 co-expression, intrinsic chemotherapy resistance, and poor survival. The prognostic utility of TREM1 (cutoff > 21%) may enhance risk stratification, while its immunomodulatory function underscores its potential as a therapeutic target. Future studies should validate these findings in larger, multiethnic cohorts and explore the mechanistic links between TREM1 and AML pathogenesis.

Both patients failed to achieve remission after CAR-T cell therapy, but bone marrow examination following therapy revealed the elimination of FLT3+ AML blasts, persistence of FLT3 - AML blasts, and early post-treatment preservation of normal CD34+ hematopoietic stem and progenitor cells (HSPCs) with variable FLT3 expression. Collectively, autologous FLT3 CAR-T cells can be safely administered and can eradicate FLT3⁺ blasts with minimal toxicity, without causing substantial damage to normal CD34⁺ HSPCs; however, they fail to induce leukemic remission due to the heterogeneity of FLT3 expression and the persistence of FLT3⁻ AML blasts.