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Role of Proliferation in the Pathogenesis of T-cell Acute Lymphoblastic Leukemia In spite of successful management of children with acute lymphoblastic leukemia (ALL), a fifth of diagnosed patients relapse after induction treatment. We propose to test the hypothesis that a deregulated response to childhood infections can induce expansion of pre-leukemic cells and overt leukemia. We […]

Detecting blocks in Apoptosis in Leukemia Stem Cells Cancer biologists are beginning to appreciate that at least in some cancers, including acute myelogenous leukemia (AML), there are certain special cells, called “cancer stem cells”. These cancer stem cells can repopulate the entire cancer, and cure will likely require the eradication of these cells. Dr. Letai […]

Identifying stop codon-generated minor histocompatibility antigens capable of eliciting potent GVL or GVHD alloresponses Minor histocompatibility antigens (mHAgs) are molecules on the surface of cells that differ between donor and recipient during allogeneic hematopoietic cell transplantation (HCT), and can elicit either a potentially curative graft-versus-leukemia (GVL) effect or life-threatening graft-versus-host disease (GVHD). Effectively separating GVL […]

Characterization of Cannabidiol (CBD) as a Novel Therapy for Mantle Cell Lymphoma Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with a high rate of relapse after currently available treatments. Novel therapeutic strategies are urgently needed for patients who relapse. Recent studies indicate that cannabidiol (CBD), a potent, non-psychotropic component of the plant […]

The Development of Murine Models of Recurring Myeloid Leukemia-Associated Chromosomal Deficiencies Tumor cells in patients with leukemia or lymphoma frequently have abnormal chromosomes. There are recurring abnormalities that typify certain kinds of malignancies. Deletions of parts of chromosomes 5 and 7 are common in patients that develop leukemia months or years after treatment for other […]

The Role of Rituximab in Allogeneic Hematopoietic Cell Transplantation for B-Cell Non-Hodgkin Lymphoma Non-Hodgkin lymphoma (NHL) is an increasingly common cancer. For many patients, the only potentially curative treatment is blood stem cell transplantation. However, such transplants can fail either because of lymphoma recurrence or because of complications such as graft-vs.-host disease. Dr. Rezvani’s research […]

Targeting Inflammation Within The Tumor Microenvironment for Cancer Therapy Inflammation is a key determinant of cancer progression. Dr. Beatty’s research uses a mouse model of cancer that faithfully reproduces inflammation within the tumor microenvironment as is seen in human cancers. Using this model, he has found that macrophages linked to cancer can be therapeutically targeted […]

Identifying vulnerabilities in hematologic malignancies driven by heterotrimeric G proteins Blood cancers arise from cells that acquire mutations before becoming a leukemia. We study a gene called GNB1 that is often mutated in patients with “pre-leukemic” blood cells, and in leukemia and lymphoma. We will determine how best to target GNB1 mutant cells to treat […]

Molecular Rationale for WNT Inhibitor Therapy in B-Cell Lymphoma The FOXP1 protein is overexpressed in B-cell lymphomas, and patients with high FOXP1 levels often resist therapy and are given a poor prognosis. We discovered that FOXP1 activates the WNT signaling pathway. We will determine whether WNT inhibitors currently in clinical trails for other cancers will […]

An Integrative Approach to the Control of Intractable Pain from Cancer such as Multiple Myeloma The relief of suffering is a high priority for patients with cancer and their families. Advanced cancers frequently cause severe chronic pain because of cancer spread to the bones and internal organs. Progress in pain treatment has been achieved over […]

Dynamic Changes in MDS Clonal Architecture During Treatment with Hypomethylating Agents

The Role of Mutations in Epigenetic Regulators in Myeloid Leukemia Cure rates for AML patients have not substantially improved in the last 40 years. To keep pace with the genomics revolution, the focus of this project is to develop model systems that more closely resemble the natural history of cancer to understand how different mutations […]