Targeting Valine-Specific Amino Acid Dependency -in T-Cell Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer with more than 3,000 children/adolescents under the age of 20 diagnosed with ALL each year in the United States. It mostly afflicts children between the ages of three and five. ALL is a disease that affects a type of white blood cells called lymphocytes that help the body fight infection and disease. ALL is characterized by the presence of large number of immature/non-functional lymphocytes which accumulate in the spleen, bone marrow and lymph nodes. ALL can be broadly divided into either B-ALL or T-ALL. B-ALL affects a type of lymphocytes called B-lymphocytes whereas T-ALL affects T lymphocytes. Historically, children with T-ALL have worse prognosis than B-ALL. B-ALL also have better therapeutic options available including targeted and immunotherapies, whereas children with T-ALL are limited to therapies with well-documented long-term negative effects like chemotherapy (using medicines to kill leukemic cells), and radiation therapy (using high energy radiations to kill leukemic cells). Hence, better targeted therapies that kill leukemic cells without harming normal cells are the need of the hour in T-ALL.
In this proposal, I aim to evaluate a novel therapeutic approach of nutrient deprivation to treat T-ALL grounded on my preliminary finding that T-ALL cells need high levels of amino acid valine for their growth and survival. Based on this evidence, this proposal explores whether dietary reduction of valine can lead to a better targeted therapy for children affected with T-ALL.