Targeting Genetic and Metabolic Networks in T-ALL

T-lineage acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that requires treatment with unusually strong chemotherapy. Despite recent progress in the treatment of this disease, 25% of children and 40% of adults with T-ALL are either unresponsive or respond only transiently to chemotherapy and ultimately fail to be cured. Further treatment advances require the development of effective and highly specific molecularly targeted therapies. The aim of this project is to identify key genes that are essential for the proliferation and survival of T-ALL cells. To achieve this goal, Dr. Ferrando is using emerging technologies to compile a complete catalog of genetic alterations responsible for the pathogenesis of T-ALL in order to analyze how these mutations impact the complex and intricate circuitries that control leukemia cell growth, proliferation, and survival. This T-ALL network, essentially a road map of how T-ALL mutations work and how they interact with one another, will facilitate the identification of key genes and pathways. Selective inhibition of these genes will identify targets for the development of new, more active, and highly specific anti-leukemic drugs. This project represents a unique opportunity to exploit genomic technologies and develop new approaches to identify targeted therapies that will ultimately be applicable to a broad spectrum of cancers.