Childhood Cancer

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Dissecting Metabolic Vulnerabilities of Relapsed ALL

Institution: 
University of Southern California
Researcher(s): 
Betty Yingchun Shen
Grant Type: 
POST Program Grants
Year Awarded: 
2018
Type of Childhood Cancer: 
Acute Lymphoblastic Leukemia (ALL)
Project Description: 

Background
The primary goal of this project is to investigate biochemical profiles of secreted and non-secreted metabolites specific to relapse in B-lineage childhood acute lymphoblastic leukemia (ALL) cells. Despite advances in therapy, relapsed leukemia remains the leading cause of death in children with cancer. Therefore, there is an urgent need to understand the molecular mechanisms underlying relapse, which could ultimately lead to the development of novel therapies. One of the hallmarks of cancer is reprogramming cellular metabolism to support its growth and transformation. Prior studies from the Resar lab revealed that overexpression of HMGA1 correlates with relapse in childhood leukemia and other cancers. 

Thus, we hypothesize that the overexpression of HMGA1 reprograms the metabolism of leukemia cells and drives relapse. Preliminary metabolic studies in solid tumors indicate significant differences between cancer cells overexpressing HMGA1 to those with HMGA1 silencing. Moreover, blocking HMGA1 metabolic function could be effective therapy to prevent or treat relapsed leukemia. Based on these results, we hypothesize that: 1) overexpression of HMGA1 induces metabolic changes that promote relapse in pediatric ALL; 2) reprogrammed metabolic pathways could be targeted as novel therapy for at least a subset of relapsed ALL. 

Project Goal
To test these hypotheses, we propose the following aims: 1) To identify metabolites and metabolic profiles induced by HMGA1 that drive relapse in ALL using cell lines derived from children with relapsed ALL; 2) To use in silico algorithms to identify metabolic vulnerabilities that could be targeted in therapy. This work could open the door to a new therapy for relapse in childhood ALL.

Mentored by Dr. Linda Smith Resar 
Johns Hopkins University School of Medicine, Baltimore, MD

Co-funded by: 
Love Your Melon