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Knight Cancer Pilot Project Awardees: Anupriya Agarwal, Ph.D. and Grover Bagby, M.D. Share This OHSU Content

Anupriya Agarwal, Ph.D., Research Assistant Professor, Leukemia Center and Grover Bagby, M.D., Professor, Hematology & Medical Oncology 

Knight Cancer Institute Cancer Center Support Grant

Title: "Acute Myelogenous Leukemia: Targeting IL-1 dependent leukemia cell growth"

Abstract:Acute myeloid leukemia (AML) represents the most common type of leukemia and remains an unresolved health problem in pediatric and adult populations. It is often progressive and fatal with a five-year median survival of less than 30% with conventional chemotherapy. Despite the great strides that have been made toward the treatment of AML patients, one-third of patients have resistant disease and eventually succumb to their leukemia. Cytotoxic chemotherapy has remained the mainstay of AML treatment for decades, so more rationally designed targeted therapies are needed. Clinically, the most successful example of targeted therapy has been the treatment of chronic myeloid leukemia (CML) patients with imatinib, which targets the disease-causing fusion gene, BCR-ABL. In contrast, the treatment of AML had been challenging because the molecular abnormalities in AML cells are more complex and more heterogeneous than those found in CML cells. Numerous genetic changes are reported but their clinical relevance is not always well defined. Recently, selective inhibitors have been developed for many genes and pathways that are altered in AML. However, successful implementation of treatment with these agents is impeded due to incomplete understanding of the genetic changes driving this disease process.This current state underscores the need for the identification of candidate target genes and signaling pathways driving AML so that specific targeted therapy can be tailored for these patients. We have identified that Interleukin-1 (IL-1) signaling pathway is actively involved in the proliferation of leukemia cells derived from AML patients. The proposed study is designed to clarify the molecular basis of this aberrant pathway and to target it therapeutically. This knowledge will improve our understanding of AML pathophysiology and will provide innovative strategies for targeting this pathway.

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