Researchers may have identified how low levels of the TET2 gene may fuel rapid cancer growth in patients with acute myeloid leukemia (AML), according to a recent study published by Li et al in Cell Stem Cell.
AML is distinguished by the rapid division and metastasis of immature leukemia stem cells. More than 50% of patients who are treated for leukemia relapse, and the 5-year survival rate is 30%. Figuring out how to destroy these cells may be crucial to effectively treating the disease.
TET2 deficiencies cooperate with leukemia-related oncoproteins resulting from chromosomal abnormalities or gene mutations to drive the development of leukemia and enhance the malignant stem cells’ ability to divide and metastasize. Prior to the new study, the cellular and molecular mechanisms underlying these processes were uncertain.
Study Methods and Results
In this study, the researchers analyzed data from The Cancer Genome Atlas and discovered that the expression or mutation of TET2 was associated with poorer prognoses and shorter overall survival rates for patients with AML. Compared with healthy controls, TET2 expression was significantly suppressed in patients with AML.
The researchers also determined that TET2 deficiencies were capable of setting off a cascade of biochemical changes that enhanced AML’s ability to metastasize. Among the changes were:
By expanding the understanding of the multiple ways in which TET2 may influence the development of AML, the recent findings suggest new potential therapeutic targets for treating patients with the disease.
“This study provides novel insights into the cellular and molecular mechanisms underlying the development of [AML],” emphasized senior study author Jianjun Chen, PhD, the Simms/Mann Family Foundation Chair in Systems Biology at the Beckman Research Institute at the City of Hope. “Our findings highlight the therapeutic potential of reactivating TET2 signaling in patients with TET2 mutations or transcriptional suppression. Equally exciting, this strategy could be applied to other types of cancer that feature TET2 deficiencies,” he concluded.
Disclosure: The research in this study was partly supported by grants from the National Institutes of Health, the Simms/Mann Family Foundation, Leukemia Research Foundation New Investigator Research Grant, The Margaret E. Early Medical Research Trust, and the American Association for the Study of Liver Diseases Foundation. For full disclosures of the study authors, visit cell.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.