Hogge, Donna E. MD, PhD, FRCPC
Director, VGH Cell Separator Unit
Clinical Professor, Medicine, UBC
Member, Genetics Program, UBC
Member, Experimental Medicine Program
Associate Member, Pathology and Laboratory Medicine
Member, Leukemia Bone Marrow Transplant Program of BC
Research Interests
Growth Factors, Leukemia, Gene Transfer, Megakaryocytopoiesis, Molecular regulation of normal and malignant human hemopoiesis
The maintenance of adequate numbers of functional blood cells is a complex process involving regulation of cell growth, maturation and ultimately cell death. The precise way in which the orderly production of these cells is controlled in vivo in man is unknown, although many regulators have now been identified.
Normal growth responses are often perturbed in leukemic blood cells and disordered regulation of cell proliferation and maturation are hallmarks of all human hematologic malignancies. The goal of my research is to understand normal regulatory mechanisms and the abnormalities that result in malignant transformation.
The ability of specific hemopoietic regulators to support or inhibit the maintenance and growth of primitive normal and malignant hemopoietic cells is being investigated in vitro and in vivo. Culture conditions which support the growth of hemopoietic cells are modified by the addition or removal of specific regulatory factors and the effects assessed over time. Specific conditions have been developed which allow the growth and manipulation of primitive malignant progenitors for patients with acute leukemia and normal progenitors of the megakaryocyte lineage.
Immunodeficient mice provide convenient hosts for the growth of normal and leukemic human hematopoietic cells. These mice are also used to explore mechanisms of growth regulation in leukemic and normal cells and provide a preclinical system for testing of novel therapeutic strategies that may be effective in the treatment of leukemia in man.
Ultimately it is hoped that these studies will lead not only to improved understanding of basic growth control of hemopoietic cells but also to improved results in the treatment of leukemia and the use of bone marrow transplantation in man.
Selected Publications
Hogge DE, Lansdorp PM, Reid D, Gerhard B, Eaves CJ. 1996. Enhanced detection, maintenance and differentiation of primitive human hematopoietic cells in cultures containing murine fibroblasts engineered to produce human Steel factor, interleukin-3 and granulocyte colony-stimulating factor. Blood 88:3765-3773
Hogge D, Fanning S, Bockhold K, Petzer A, Lambie K, Lansdorp P, Eaves A, Eaves C. 1997. Quantitation and characterization of human megakaryocyte colony-forming cells using a standardized serum-free agarose assay. Br. J Haematol 96:790-800
Ailles LE, Gerhard B, Hogge DE. 1997. Detection and characterization of primitive malignant and normal progenitors in patients with acute myelogenous leukemia using long-term coculture with supportive feeder layers and cytokines. Blood 90:2555-2564
Hogge DE, Willman CL, Kreitman RJ, Berger M, Hall PD, Kopecky KJ, McLain C, Tagge EP, Eaves CJ, Frankel AE. 1998. Malignant progenitors from patients with acute myelogenous leukemia are sensitive to a diphtheria toxin-granulocyte-macrophage colony-stimulating factor fusion protein. Blood 92:589-595
Ailles LE, Humphries RK, Thomas TE, Hogge DE. 1999. Retroviral marking of acute myelogenous leukemia progenitors that initiate long-term culture and growth in immunodeficient mice. Exp Hematol. 27(11):1609-20
Ailles LE, Gerhard B, Kawagoe H, Hogge DE. 1999. Growth characteristics of acute myelogenous leukemia progenitors that initiate malignant hematopoiesis in nonobese diabetic/severe combined immunodeficient mice. Blood 94(5):1761-72