The following is a summary of “Key role of glutamine metabolism in persistence of leukemic cells upon exposition to FLT3 tyrosine kinase inhibitors.,” published in the June 2024 issue of Hematology by Khamari et al.
Acute myeloid leukemia (AML) poses significant challenges in clinical management due to its aggressive nature and propensity for relapse despite advancements in treatment strategies. The discovery of FLT3 gene mutations has been pivotal, leading to targeted therapies like Quizartinib, which inhibit these oncogenic pathways. However, achieving complete remission with FLT3 inhibitors remains problematic as a subset of leukemic cells persistently evade treatment, ultimately developing resistance. The research delved into understanding the metabolic adaptations of these resilient leukemic cells during Quizartinib therapy. Through comprehensive biochemical and metabolomics analyses, the researchers uncovered that these cells rely heavily on mitochondrial metabolism, mainly through glutamine oxidation, to survive treatment pressures.
The study highlighted a crucial finding: the synergistic efficacy of combining Quizartinib with L-asparaginase, a drug known for its anti-metabolic properties. This combination therapy demonstrated efficacy in targeting and eradicating the Quizartinib-resistant leukemic cells in experimental models; by exploiting metabolic vulnerabilities, particularly the dependency on glutamine metabolism, the study group aimed to disrupt the survival mechanisms of these persistent leukemic cells. This approach offers a novel strategy to mitigate resistance to FLT3 inhibitors and suggests a pathway to enhance treatment outcomes in patients with AML.
Furthermore, the findings underscore the importance of integrating metabolic studies into developing therapeutic strategies for AML. By elucidating how leukemic cells adapt metabolically under treatment pressure, they provide insights into potential avenues for improving treatment efficacy and overcoming therapeutic resistance. This research contributes to a broader understanding of the intricate interplay between cancer biology and metabolic pathways, paving the way for innovative approaches to personalized medicine in leukemia treatment.
Source: sciencedirect.com/science/article/pii/S0301472X24001127