In a recent article in Nature, researchers from the universities of Georgia and Tokyo have presented a new molecular mechanism that drives disease progression in myeloid leukemia. The researchers have been able to stop cancer cell growth in mice as well as human blood samples from leukemia patients in the acute or blast crisis phase of the disease.
The key driver in this mechanism is a protein called BCAT1 which activates the metabolism of a group of amino acids known as branched-chain amino acids, or BCAAs. These are essential building blocks of proteins in all cells and thus necessary for aggressive leukemia cells to grow. BCAT1 when activated by another gene, MSI2, kicks of a metabolic pathway where BCAAs are produced through a process called reamination.
The most groundbreaking aspect of this finding is the fact that until this paper, it was assumed that BCAAs are not produced within the body. The BCAT - MSI1 interaction now adds a new and important mechanism that drives tumor growth.
A key question as this point is how the BCAT1-MSI2 pathway may play a role in other cancers beside myeloid leukemia. Using the Euretos Knowledge Platform, 17 types of cancer were identified that have both BCAT1 and MSI2 expression. However, only 10 of these disorders also have annotations for the involvement of BCAAs in the disease pathology:
Figure 1: Types of cancer with BCAT1 and MSI2 expression and interaction with BCAAs (source: Euretos Knowledge Platform)
The 10 types of cancer that may also be impacted by the BCAT1/MSI2 pathway are: endometrial cancer, urinary bladder cancer, colorectal carcinoma, glioma, breast cancer, prostate cancer, pancreatic carcinoma, ovarian carcinoma, lung cancer and stomach cancer. Four of these (in italic) are also mentioned in the article.
For these 10 disorders, tumor expression data from the Human Protein Atlas, one of the sources integrated in the Euretos Knowledge Platform, was analysed which enabled a ranking based on the percentage of the population with medium/high BCAT1 and MSI2 expression.
Table 1: Percentage of tumors with medium to high BCAT1 and MSI2 expression (source: Human Protein Atlas)
Based on these tumor expression values it would seem that especially most endometrial cancer, urinary bladder cancer and glioma patients could be affected by this mechanism. Also widely occurring neoplastic disorders such as colorectal, breast and prostate cancer involve over 60% of patients. Further research into whether the BCAT1-MSI2 mechanism is relevant for these disorders seems highly relevant.
In this research effort it is important to distinguish between the potential role of the three BCAAs, valine, leucine and isoleucine as they may not be involved in each type of cancer. Especially leucine seems least involved based on known literature and disease annotations.
Figure 2: Involvement of the BCAAs Leucine, Isoleucine and Valine in cancers with BCAT1 and MSI2 expression (source: Euretos Knowledge Platform)
This new mechanism seems very promising and may play a role in addressing especially the most dangerous phase of disease acceleration.
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About this series - The purpose of the Euretos Research Note series is to provide a data analytics perspective on recent life sciences publications. The series focuses on two types of questions: (1) Did the available data already point in the direction of a discovery? (2) What further research angles does the available data suggest?.