Inducing Leukemia Cell Death Through the Inhibition of Amino Acids

By Riya Gandhi ‘22

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Figure 1. Amino acids are often referred to as the “building blocks of life”.

Thanks to chemotherapy, acute myeloid leukemia (AML) is not the most fatal kind of cancer. However, the same chemotherapy that treats the disease may also revitalize leukemia stem cell populations, thereby increasing the probability of relapse. As such, scientists are still actively researching alternative treatments and cures. Most recently, researchers looked into the importance of amino acids for preventing the growth of leukemia stem cells (LSC).

At University of Colorado’s Division of Hematology, principle investigator Courtney L. Jones and her team of researchers conducted an experiment to study the role of amino acids for leukemia stem cells. First, they isolated enriched LSCs using reactive-oxygen-species (ROS) and profiled those that were low in ROS using mass spectroscopy. In doing so, the researchers discovered that metabolites were significantly higher in the ROS-low LSCs and that amino acid metabolism was also enriched in these same cells. Next, they documented the uptake of amino acids and the resulting metabolism to uncover the role of amino acids. Afterwards, they noticed that, once again, the ROS-low LSCs used more amino acids. To test if LSCs were dependent on amino acids for survival through a process of measuring cell viability and colony-forming potential, the researchers implanted grafts with and without the amino acids into the cells. Ultimately, the data suggested that that leukemia stem cells are dependent on amino acids for survival. When the researchers inhibited amino acid metabolism, they determined that oxidative phosphorylation decreased, thereby inducing cell death; however, LSCs taken from relapse patients demonstrated no need for amino acids.

In general, the findings of these researchers indicated that LSCs can be eliminated using amino acid vulnerability as a biomarker. With time, scientists may be able to take this knowledge and apply it to other forms of cancer. For now, this discovery will certainly aid in developing better treatments for AML.

 

References

  1. C. Jones, et. al., Inhibition of amino acid metabolism selectively targets human leukemia stem cells. Cancer Cell 34 (2018). doi: https://doi.org/10.1016/j.ccell.2018.10.005.  
  2. Image retrieved from: https://www.pexels.com/photo/clinic-doctor-health-hospital-40559/
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