Birgit Knoechel, MD, PhD
2015-2017
Project: Epigenetic Mechanisms of Resistance in T-cell Acute Lymphoblastic Leukemia
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Acute t-cell lymphoblastic leukemia (T-ALL) makes up about 15-20% of leukemia diagnoses in children and adolescents. T-ALL has high rates of relapse and is often resistant to treatment. When a child with T-ALL relapses or has toxicity problems and cannot tolerate standard chemotherapy treatments, there are almost no alternative treatment options.
Dr. Birgit Knoechel at Dana-Farber Cancer Institute is trying to change the odds for children and young adults with T-ALL. Her research examines new epigenetic targets for this disease. Epigenetics is the study of information in a cell that is not encoded in the DNA but can be maintained and passed on through cell division. In cancer cells, epigenetic marks communicate a kind of cellular “memory.” Although it is difficult to target cancer genes, it is possible to target epigenetics and, by doing so, create innovative and less toxic treatments for cancer. These targeted treatments present a much-needed alternative for children in whom standard therapy has failed. Dr. Knoechel is exploring the role of EZH2, an enzyme that is overexpressed in a number of cancers. When this enzyme is overexpressed, it silences genes that control cancer growth, allowing tumor cells to grow and spread. Since a number of FDA-approved compounds already exist to target EZH2, this research could be translated quickly to clinical trial.
As the result of this project, Dr. Knoechel has made significant contributions to the understanding of epigenetics in T-ALL:
- 4 novel cell models developed
- 3 compounds tested for treatment of T-ALL
- 5 T-ALL primagrafts (models developed by injecting patient T-ALL cells into mice) established