DNA Methylation As a Target for Prognosis and Treatment of Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL), has the greatest prevalence rate among all leukemias. A significant limitation of both the existing staging systems for CLL is that they do not allow for reliable prediction of the rate of disease progression, or which patients are likely to respond to specific treatment. This work shows that the global DNA methylation index is a prognostic market for CLL, which can predict disease progression and response to specific therapies.
Hypermethylation contributes to disease progression by suppressing apoptosis and increasing cell proliferation through silencing of tumor suppressor genes. Higher levels of DNA methylation are a predictor of more rapid CLL progression, and indicate that the patient is likely to require systemic therapy. Early clinical studies show that DNA methylation levels are predictive of a favorable clinical response to treatment by DNA methylation inhibitors. Determination of global DNA methylation levels can be combined with other prognostic approaches to CLL, including determination of methylation of specific tumor suppressor genes, expression level of specific biomarkers (Zap-70, CD38), detection of specific microRNAs, or presence of chromosomal alterations.
CLL is the most commonly diagnosed form of adult leukemia in the Western world, accounting for up to 35% of all adult leukemias. This technology provides an approach to predict which patients require aggressive treatment and response to specific therapies.
Stage of Development
Patent applications have been filed and are pending in the United States, Europe, and Japan. This technology is part of an active and ongoing research program. It is available either for developmental research support or licensing.
u, M.K, et al. �Progressive disease in chronic lymphocytic leukemia is correlated with the DNA methylation index.� Leukemia Research. 2007. 31:773-777.
� Yu, M.K. �Epigenetics and chronic lymphocytic leukemia.� Am. J. Hematology. 2006. 81:864-869.
� Ongoing clinical trials at the Huntsman Cancer Institute (www.hci.utah.edu) focus on further exploration of how DNA methylation contributes to CLL, and which drugs affect disease progression.
John Phillips, Margaret Yu
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