Program Leader Kevin Shannon, MD

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The goal of the Cancer Center's Hematopoietic Malignancies Program is to improve the care of patients with leukemia and lymphoma through focused research efforts.

The program includes 35 faculty members from nine academic departments within the university. The origins of this program date from the mid-1970s, with the discovery of oncogenes by UCSF researchers J. Michael Bishop and Harold Varmus, and the pioneering work of Y.W. Kan, which established the underlying genetic lesions in a number of human hematologic disorders. Since that time, UCSF investigators have made novel contributions in diverse areas such as using stem cell transplantation in the front-line treatment of adult hematologic malignancies; elucidating the molecular genetic basis of leukemia and lymphoma; characterizing the role of initiating lesions in maintaining the tumorigeneic phenotype; and understanding how hematopoietic cells regulate survival, proliferation, and differentiation in response to growth factors and chemokines.

Two principles guide this multidisciplinary program. The first is that clinical aspects of leukemia and lymphoma can inform basic research and, conversely, that these laboratory investigations will ultimately lead to improved patient care. Second, studies of how normal hematopoietic cells regulate growth, differentiation, and death are integral to understanding how these processes are perturbed in neoplasia. Applying this philosophy to the problem of hematopoietic cancer has resulted in a program that includes clinical, translational, epidemiologic, and basic investigators who are utilizing diverse approaches to conduct studies in normal and malignant hematopoietic cells.

Characterizing how normal physiologic processes are perturbed in leukemia and lymphoma will provide a scientific foundation for rational new strategies to diagnose, prevent, and treat these cancers. Because the molecular alterations that contribute to leukemia and lymphoma are relatively well understood, these malignancies provide exceptional opportunities to develop animal models for testing new treatment strategies. UCSF investigators have generated a number of relevant mouse models, which are being used to elucidate targets for rational therapeutic intervention and to perform translational preclinical trials. The Hematopoietic Malignancies Program includes efforts directed at gene discovery, modeling leukemia and lymphoma-associated genetic lesions in the mouse, characterizing signal transduction pathways that are crucial for cellular growth control, testing experimental therapeutics, and defining inherited and environmental risk factors that contribute to the development of hematologic cancers.

The program is built upon extraordinary institutional strengths in basic and population sciences, outstanding clinical programs for the care of adults and children with leukemia and lymphoma, and a tradition of cross-disciplinary collaborations in scientific investigations. These resources are used to:

• develop more effective and less toxic therapeutics for hematopoietic cancers that are based on an increased understanding of molecules that regulate the growth, differentiation, and death of these cells;

• characterize the functions of genes and proteins that are critical for the normal growth of immature and lineage-committed hematopoietic cells;

• develop and exploit animal models for biologic and preclinical therapeutic studies; and

• investigate the genetic and environmental causes of leukemia and lymphoma.