T-lineage acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that requires treatment with intensified chemotherapy. Despite recent progress in the treatment of this disease, 25 percent of children and 40 percent of adults with T-ALL show primary resistant leukemia 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 drugs. This project will identify key genes that are essential for the proliferation and survival of T-ALL cells. To achieve this goal, Ferrando will use emerging technologies to compile a complete catalog of genetic alterations responsible for the pathogenesis of T-ALL and to analyze how these mutations impact the circuitries that control normal cell growth, proliferation and survival. He will analyze the effects of cancer mutations in the complex and intricate circuitries that control leukemia cell proliferation and survival. This T-ALL network represents a roadmap of how T-ALL mutations work and how they interact with each other and 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 antileukemic 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.
Adolfo A. Ferrando, M.D., Ph.D., is assistant professor of pediatrics and pathology at Columbia University.
Updated: April 4, 2011