NOTE
🌱 created from: AML
flt3_mutation_in_aml
Acute Myeloid Leukemia (AML) is a complex and aggressive blood cancer characterized by the proliferation of myeloid precursor cells. Among the various genetic factors influencing AML, mutations in the FLT3 gene (Fms-like tyrosine kinase 3) are particularly significant, affecting approximately 30% of patients. These mutations can be categorized into two main types: internal tandem duplications (FLT3-ITD) and point mutations in the tyrosine kinase domain (FLT3-TKD) [1][3].
FLT3 Mutations and Their Impact
Clinical Implications
FLT3 mutations are linked to adverse clinical features, including elevated white blood cell counts and increased blast percentages. They serve as independent prognostic factors, indicating poorer survival outcomes and lower remission rates in AML patients [1][2]. The presence of FLT3-ITD mutations, in particular, necessitates careful risk stratification and may influence treatment decisions, including the consideration for allogeneic hematopoietic stem cell transplantation (alloHCT) [2][3].
Treatment Strategies
Targeted Therapies
The treatment landscape for FLT3-mutated AML has evolved significantly with the introduction of FLT3 inhibitors:
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Midostaurin: A first-generation FLT3 inhibitor, it has been shown to improve overall survival when combined with standard chemotherapy for newly diagnosed FLT3-mutated AML patients [2][4].
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Gilteritinib: A second-generation FLT3 inhibitor, it is particularly effective for patients with relapsed or refractory FLT3-mutated AML. It has demonstrated higher complete response rates compared to traditional salvage chemotherapy [3][4].
Current Guidelines
Current treatment protocols emphasize the importance of molecular testing for FLT3 mutations at diagnosis. The incorporation of FLT3 inhibitors into treatment regimens is recommended to enhance remission rates and overall survival [3][5]. The use of combination therapies, including FLT3 inhibitors with other agents, is being explored to overcome resistance and improve patient outcomes [5].
Conclusion
FLT3 mutations play a critical role in the pathogenesis and prognosis of AML. Understanding their implications is essential for optimizing treatment strategies and improving survival rates in affected patients. Ongoing research and clinical trials continue to refine therapeutic approaches, with the aim of developing more effective and personalized treatment options for patients with FLT3-mutated AML [1][2][3].
Citations: [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590537/ [2] https://www.nature.com/articles/s41408-023-00839-1 [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607239/ [4] https://www.nature.com/articles/s41408-021-00495-3 [5] https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.612880/full [6] https://www.mdpi.com/2072-6694/15/8/2312 [7] https://www.cancer.gov/news-events/cancer-currents-blog/2023/fda-vanflyta-aml-flt3 [8] https://ashpublications.org/ashclinicalnews/news/7853/FLT3-Mutated-AML-Responds-Favorably-to-Triplet