Research Program Two:  Molecular Genetics and Hematopoiesis

Program Leaders:  Wendy Stock, MD, and Michael Thirman, MD

Overview and Scientific Goals

Cytogenetic and molecular analysis of hematological malignant diseases has led to the identification of many genes that are involved in normal hematopoiesis, as well as in the pathogenesis of leukemias and lymphomas. Members of this program have had major roles in these efforts over the past 30 years. The identification of the genetic pathways leading to hematological malignant diseases has important biological implications, as well as ramifications for diagnosis and treatment of these diseases.

The Molecular Genetics and Hematopoiesis Program is comprised of a tightly-integrated group of 26 members from five academic departments who are linked by common research themes.  The primary research goals of the investigators in the Program are to

        • investigate mechanisms of normal and malignant hematopoiesis and to elucidate pathogenetic pathways in hematologic cancers through the study of recurring chromosomal and molecular genetic aberrations in human leukemias and lymphomas;
        • generate and analyze model systems to dissect the functions of genes that are critical to normal hematopoiesis and to the development of hematopoietic diseases; and
        • translate these insights into the design of novel risk-adapted clinical trials.

In recent years, insights gained related to these goals have begun to be translated into novel molecularly targeted therapeutic approaches for hematological malignancies.

Program Highlights 2005 – 2007

  • Dr. Thirman and colleagues were awarded a $5.25 million Specialized Center of Research (SCOR) grant from the Leukemia and Lymphoma Society of America.  The goal of the SCOR, entitled "Peptide and Small Molecule Therapeutics for Hematologic Malignancies," is to develop a comprehensive multidisciplinary program that will provide a platform for the identification and testing of novel cell-permeable peptides and small molecules for the treatment of hematologic malignancies. This SCOR proposal brings together a large group of scientists to form a highly interactive group of chemists, molecular biologists, and clinicians who might not otherwise have the opportunity to work together in a translational research program in leukemia and lymphoma. This SCOR encompasses a collaborative effort involving ten University of Chicago senior researchers and two project leaders from other NCI-designated Cancer Centers.
  • In February, 2007, Drs. Vardiman and Le Beau sponsored an international meeting of the original group of investigators who prepared the World Health Organization’s “Classification of Tumors of the Hematopoietic and Lymphoid Tissues”. These investigators met to revise and refine the WHO classification, focusing on the incorporation of new molecular genetic markers of disease. This meeting was sponsored, in part, by the UCCRC. The publication of the revised WHO Classification is planned for early 2008.

  • Drs. Odenike, Smith, Stock, van Besien, Zimmerman have established an experimental therapeutics program for hematologic malignancies. 

  • Drs. Stock and Nachman have demonstrated that adolescents/young adults with ALL have distinct outcomes depending upon treatment on pediatric or adult cooperative group clinical trials for ALL.

  • In an example of the success of molecularly targeted therapy in cancer, Dr. Larson and colleagues from around the world (the IRIS investigators) have conducted the key clinical trials that resulted in approval of imatinib (a targeted BCR-ABL tyrosine kinase inhibitor) as front-line therapy for CML. They have demonstrated that the majority of chronic phase CML patients will achieve complete cytogenetic responses following imatinib treatment and that these responses are durable (Druker et al. N Engl J Med 2006).

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Links

Program 1
Cell Signaling and Gene Regulation
Program Leaders: Marsha Rosner, PhD and Suzanne Conzen, MD

Program 2
Molecular Genetics and Hematopoiesis
Program Leaders: Wendy Stock, MD and Michael Thirman, MD

Program 3
Immunology and Cancer
Program Leader: Thomas F. Gajewski, MD, PhD

Program 4
Clinical and Experimental Therapeutics
Program Leaders: Everett E. Vokes, MD and M. Eileen Dolan, PhD

Program 5
Advanced Imaging
Program Leaders: Maryellen L. Giger, PhD and Heber MacMahon, MD

Program 6
Cancer Risk and Prevention
Program Leaders: Olufunmilayo (Funmi) I. Olopade, MBBS and Andrea King, PhD