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Establishing the Function of Novel MicroRNAs Associated with Resistance and Relapse in Pediatric AML

Institution: 
Fred Hutchinson Cancer Research Center
Researcher(s): 
Vivian Oehler, MD & Soheil Meshinchi, MD/PhD
Grant Type: 
Innovation Grants
Year Awarded: 
2017
Type of Childhood Cancer: 
Acute Myelogenous Leukemia (AML)
Project Description: 

Background
Acute myeloid leukemia (AML) is a highly lethal cancer. Although survival rates have improved over the last decades, about half of children and young adults with AML don't respond to therapy or relapse even after the most intensive available treatment. More effective therapies are urgently needed. In the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) project we have applied the first and most comprehensive approach to identify the molecular alterations that contribute to therapy resistance and relapse in pediatric patients. Our overarching goal is to advance new diagnostics and novel individualized treatments that will improve patient outcomes. MicroRNAs (miRNAs) are small molecules that negatively regulate specific gene expression. Our TARGET discovery studies showed that miRNAs can be used as diagnostic biomarkers to identify patients for whom standard chemotherapy is likely to fail and have identified miRNAs that contribute to relapse or failure to respond to chemotherapy. Among this group, we have discovered miRNAs that have never been described before. It will be important to learn how these “novel” miRNAs promote leukemia evolution and therapy resistance. 

Project Goal
Our studies are designed to examine the molecular processes through which these novel miRNAs act and establish which drugs can reverse these leukemia-supportive effects. We will also examine, in a group of 900 patients, if novel miRNA expression prior to therapy identifies patients at high risk for treatment failure. Our proposed studies will improve the identification of patients who will benefit from alternative treatment strategies, identify new therapeutic targets and advance promising interventions.