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Author: Sophia
Introduction: Everyone is no stranger to acute myeloid leukemia, so we have been on the road to its treatment. Acute myeloid leukemia, as a malignant hematological disease that seriously endangers human health, its incidence rate increases with age. Finding a treatment for this disease is a direction that many researchers have been working hard on.
An article published in Nature Communications describes a specific metabolic adaptation affecting tandem mutations in the FLT 3 gene in some patients with acute myeloid leukemia. The findings suggest this could potentially be used in the future for combination treatments in certain types of patients. The study was carried out by a team led by Professor Marta Cascante from the School of Biology, Institute of Biomedical Research (IBUB) and the Network Biomedical Research Center for Liver and Digestive Diseases (CIBEREHD) of the University of Barcelona, in collaboration with Professor Jan Jacob Schuringa.
https://www.nature.com/articles/s41467-022-29639-0
Vast genetic and metabolic variability in acute myeloid leukemia
01
Acute myeloid leukemia (AML) is a disease with high genetic, clinical and metabolic variability. A qualitative pathological disease that hinders the success of currently available treatments. Specifically, FTL3 internal gene duplication (FLT3-ITD+) represents the most prevalent mutation in AML patients and is associated with high relapse rates in these patients.
This new study defines a new specific metabolic profile associated with patients with the FLT3-ITD+ phenotype. To obtain the research results, the team applied innovative technologies such as metabolomics , proteomics and stable isotope resolved metabolomics (SIRM). The research team found that the leukemia cells of these mutant patients exhibited high levels of succinate-CoA ligase and high activity of the mitochondrial electron transport complex II chain, which can provide energy for cell metabolism.
Furthermore, Professor Marta Cascante from the UB Department of Biochemistry and Molecular Biomedicine points out: "This study shows for the first time that cells of this subtype of leukemia use lactate as a substrate for mitochondrial respiration. Therefore, this map of cancer cells may have important implications for the respiratory chain "In all cells, the main substrate of the mitochondrial respiratory chain is pyruvate (from glucose )," adds ICREA academic researcher Marta Cascante. and other carbohydrates and amino acids leading to pyruvate, in addition to the ketone body , glutamine and fatty acids. Overall, however, lactate has not yet been described as a substrate for mitochondrial respiration in tumor cells. "
Tailor-made drugs based on identified mutations
02
Studies have shown that if we combine complex II inhibitors (specifically TTFA and 3-NPA compounds) with inhibitors of the MCT1 lactate transporter (CHC and AZD3965), these leukemias The mitochondrial respiratory chain in cells may be inhibited on pharmacology . Marta Cascant, a researcher at
, concluded: "This better understanding of the metabolic profile of patients' leukemia cells may lead to new and innovative approaches to designing specific types of combination therapies based on mutations identified at the genetic level. Potential possibilities. Tailor-made medicine aims to create a specific treatment for each patient based on the phenotype of their tumor, This means knowing as much as possible about each patient's tumor in order to be able to provide the best treatment for their specific tumor. The best treatment option."
Significance of research
03
The team applied technologies such as metabolomics, proteomics and stable isotope resolved metabolomics (SIRM) to come up with a series of ideas, such as the FLT 3 gene, which may be used in the future. Applied to specific types of patients for combined treatment. In addition, in view of the high genetic, clinical and metabolic heterogeneity and treatment difficulties of leukemia itself, scientists continue to conduct new research and exploration based on the metabolic profile of leukemia cells, and for leukemia, early detection and early treatment is also crucial.
Reference:
https://medicalxpress.com/news/2022-07-metabolic-profile-patients-acute-myeloid.html
https://www.nature.com/articles/s41467-022-29639-0
Note: This article It is intended to introduce medical research progress and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital.
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