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  Grants Related to Breast Cancer Funded by The Leukemia & Lymphoma Society

  Career Development: Special Fellow
LISA N. SPIRIO, PHD ▄ 1998-2001
Whitehead Institute for Biomedical Research
Cambridge, MA
Deregulation of b-catenin in breast cancer, leukemia, and lymphoma

The protein, b-catenin, is part of a biochemical signaling pathway that is involved in normal development. When this pathway is disrupted in mice, breast cancer occurs. In humans, genetic alterations of b-catenin are associated with colorectal cancer and melanoma. This protein is present in the malignant cells of leukemia and lymphoma patients, but not in normal blood cells. Dr. Spirio will investigate the role of b-catenin in tumor formation. She will examine cells derived from human leukemia, lymphoma, and breast cancers to ascertain if they have mutations in the b-catenin gene. Dr. Spirio will then use molecular techniques to address the role of the mutant b-catenin gene in tumor formation in a tissue culture system using mouse and human cells. It is known that this protein has two functions, one in cell-cell adhesion, the other in regulating gene statement. She will then turn her attention to exploring how the different parts of b-catenin participate in tumor formation. These studies should provide a clearer understanding of the molecular and biochemical events that can lead to breast cancer, leukemia, and lymphoma.

Translational Research
DIANE KRAUSE, MD, PHD ▄ 1998-2001
Department of Laboratory Medicine
Yale University School of Medicine
New Haven, CT
Development of a predictive preclinical model of human hematopoietic stem cell engraftment

The rationale for bone marrow transplantation (BMT) is that patients with poor-prognosis malignancies, including lymphoma, leukemia and breast cancer, receive treatment with very high doses of chemotherapy to kill the cancer cells. However, this chemotherapy is also toxic to the bone marrow. Without replacement of bone marrow cells via transplantation, patients receiving high-dose chemotherapy would die of marrow failure caused by lack of blood cells critical for blood clotting, oxygen distribution, and immunity against infections. Despite the widespread use of BMT, the critical cells responsible for reconstituting bone marrow function after transplantation cannot be identified and assayed in the laboratory. Dr. Krause proposes to establish a definitive method for proving these cells are present and functioning well. Once the assay is proven accurate, she will then use this model to prove that the critical blood-forming stem cells survive after experimental manipulations designed to improve the outcome of patients undergoing bone marrow transplantation.

Department of Biochemistry & Molecular Biology
Columbia University Health Sciences
New York, NY
The control of organ growth and identity by homothorax, a potential leukemia gene

Homeodomain factors are proteins, expressed in similar forms in diverse animals, that play key roles in regulating normal development of the organism. Human homeodomain proteins are disrupted in several leukemia subtypes. The Homothorax (hth)/Meis family of proteins serve as co-factors for other homeodomain factors that modulate gene statement in the course of development. Fruit flies have served as a model system for the identification and characterization of homeodomain proteins. Dr. Casares has obtained preliminary evidence that in flies hth also regulates the activity of two families of signaling molecules, Wnt and TGF-b. Wnt is also found as a gene that when altered can be involved in breast and colon cancer. For example, removing hth function results in overgrowth as a function of inappropriate statement of the Wnt gene wingless. The molecular basis of these interactions will form the focus of Dr. Casares═ research. In addition, he will continue to carry out genetic screens to identify other genes that, like hth and wingless, regulate growth and patterning. The characterization of these genes will add to our current understanding of organ development

Michael Lilly MD -- 2001 ▄2004, Translational Research
Center for Molecular Biology and Gene Therapy
School of Medicine
Loma Linda University
Loma Linda, CA

Several drugs used to treat arthritis appear to have the ability to prevent or treat common cancers, such as breast, colon, or prostate tumors. Dr. Lilly has evidence that suggests these agents may also be able to kill or cripple leukemia cells. However, no studies have examined the ability of these drugs to kill chronic lymphocytic leukemia (CLL) cells in culture or in animals. In this project, several such drugs will be investigated to define the mechanisms through which they act to kill leukemia cells in test tubes. Dr. Lilly will then determine if these drugs can prevent or slow the growth of CLL in an animal model. These efforts will also include a clinical trial of these same agents to establish how they act in patients at the cellular and biochemical level and to determine their efficacy in treating CLL.

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