FLT3 mutation

This study confirmed well-known gene-disease associations in myeloid malignancies but found no significant link between parvovirus B19 infection and specific somatic mutations or disease subtypes. These findings suggest that B19 infection may be incidental, underscoring the need for larger-scale studies to clarify its clinical relevance in patients with myeloid malignancies.

In this review, we summarize the human myeloid leukemia cell lines that express mutated FLT3 and the effect of several drugs on these cell lines. Our aim in this review is to provide clinicians with a basic science understanding of human myeloid leukemia cell lines and to provide scientific researchers with the clinical implications of FLT3 signaling inhibition.

By leveraging genomic profiling and personalized engineering approaches, CAR therapies can be refined to overcome resistance and enhance precision in AML treatment. Future research should focus on integrating multiomic data to develop mutation-adapted CAR strategies, ensuring that patients receive the most effective and personalized immunotherapy.

Loss of p53 function is strongly associated with venetoclax resistance, and adding venetoclax to 5-azacitidine provides no overall survival benefit in TP53 -mutant AML. The pro-apoptotic actions of pitavastatin depend on depletion of geranylgeranyl pyrophosphate (GGPP) and can be recapitulated by inhibiting GGPP synthase or geranylgeranyltransferase-1 enzymes. These results provide a mechanistic rationale for adding pitavastatin to AML regimens to prevent or overcome venetoclax resistance.

Resistance mechanisms, particularly following venetoclax, remain a therapeutic challenge. These data support the continued use of gilteritinib beyond second-line and highlight the need for prospective studies to optimize sequencing strategies.

Here, we applied our recently developed single-cell lineage tracing method ReSisTrace to identify cells that are intrinsically resistant or sensitive to the FLT3 inhibitors midostaurin and quizartinib in AML with FLT3-ITD mutations...In addition, in an FLT3-ITD-positive AML patient-derived xenograft (PDX) mouse model, the CC-90009 and quizartinib combination showed significantly higher anti-tumor efficacy and prolonged overall survival compared to either treatment alone...Vistusertib (mTOR inhibitor), linsitinib (IGF1R and insulin receptor inhibitor), and meisoindigo (IGF1R and Src family kinase inhibitor), all inhibiting pathways parallel to or downstream of oncogenic FLT3 signaling, were predicted and validated to sensitize FLT3-mutated cell lines and primary cells to FLT3 inhibitors. Collectively, these findings demonstrate the ability of ReSisTrace to unveil pre-existing transcriptional features of treatment vulnerability in hematological cancers and elucidate strategies for enhancing FLT3 inhibitor treatment efficacy in FLT3-ITD-mutated AML.

PSP-0119 is metabolically stable, retaining 71% of parent compound at 60 minutes in human liver microsomes. In summary, IRAK4 degradation via PSP-0119 as a promising therapeutic strategy for treatment of FLT3-mutant AML.

The former partner gene is RARG, with clinical manifestations, bone marrow morphology, and immunophenotype similar to APL. The latter partner gene is HOXC13, with the characteristics of NUP98-AML patients.

Our study confirms NPM1 mutations independently predict improved survival in pediatric AML, though outcomes remain inferior to those reported from high income countries. Larger studies are needed in pediatric AML due to its rare occurrence.

For patients entering the course-2 randomisation (n=107) survival was equivalent between standard versus intensified CPX doses (P=0.565).In this population of older patients without known adverse-risk cytogenetics, DAGO2 resulted in superior survival compared to CPX. CPX did not benefit those with MDS-related mutations over DAGO2.

The subsequent generation of potent and selective inhibitors has transformed outcomes, culminating in FDA approvals of midostaurin, quizartinib, and gilteritinib. These pathways sustain measurable residual disease (MRD), the key predictor of relapse. Rational combination strategies and MRD-directed approaches are therefore essential to fully realize the curative potential of FLT3 inhibition.