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Targeting MLL-Cofactor Interaction to Selectively Block Mixed Lineage Leukemia Leukemia often occurs due to chromosomal breakage, which results in mutations that cause blood cells to grow in a disordered and uncontrolled manner. One gene that is often involved in chromosomal translocations that occur in childhood leukemia is the MLL (Mixed Lineage Leukemia) gene. Conventional chemotherapy […]

Study of the Inhibitory Role of miR-26 in the Development of MLL-associated Leukemia Approximately 10% of human acute leukemias are involved in chromosomal translocation between the MLL (mixed lineage leukemia) gene and over 50 partner genes. These leukemias occur preferentially in infant and young children and are often associated with poor outcome. MicroRNAs (miRNAs) are […]

Genomic and Functional Identification of Critical Targets in Peripheral T Cell Lymphoma Peripheral T cell lymphoma (PTCL) is a disease of increasing incidence and poor prognosis. We will combine molecular biology and genomics approaches to analyze the mutations and gene regulatory disruptions that contribute to the malignant biology of PTCL. Armed with novel mechanistic insights […]

The Bcl-6 oncoprotein as a target for transcription therapy Dr. Melnick’s research will focus on determining the mechanism of action of transcription factors (master regulatory proteins that govern the activity of the genome) involved in the molecular pathogenesis of hematologic malignancies. Dr. Melnick and his team discovered a key mechanism of action of a factor […]

The Role of ASXL1 mutations in leukemia patients The development of genomic technologies has uncovered a number of genetic abnormalities in patients with cancer, including acute myeloid leukemia (AML). In large-scale genomic studies we have found that the gene ASXL1 (Addition of Sex Combs-Like 1) is commonly mutated in AML patients. Moreover, we have identified […]

Prospective Validation and Genetic Basis of a Novel Molecular Risk Predictor for Diffuse large B-Cell Lymphoma Drug-development is time consuming and costly, consuming on average 10-years and $800-million for each drug to reach patients. We can circumvent these barriers by designing risk-adapted clinical trials testing new therapies. We developed a method for predicting outcomes for […]

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 […]