Childhood Cancer

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The Role of Tumor Heterogeneity in Relapse of Pediatric Acute Myeloid Leukemia

Institution: 
Children’s Hospital & Research Center at Oakland
Researcher(s): 
Cheryl Peretz, MD
Grant Type: 
Young Investigator Grants
Year Awarded: 
2019
Type of Childhood Cancer: 
Acute Myeloid Leukemia (AML)
Project Description: 

Background:

Acute leukemia is the most common childhood cancer  and remains highly lethal. Even with the best treatments, almost half of children with acute myeloid leukemia (AML) do not survive. Survival rates of pediatric AML have remained distressingly static for the past two decades. A key barrier to improving outcomes in pediatric AML is understanding relapsed disease, which is a major driver of mortality. Certain genetic changes, or mutations, in leukemia cells make them more likely to relapse. One of these is a mutation in FLT3, the most commonly mutated gene in pediatric AML. But leukemias have multiple mutations at the same time; how mutations work together and/or change between diagnosis and relapse is not well understood. The technology to investigate these mutations now allows us to look at mutations within a single cell. We are using this technology to teach us how pediatric AML changes to become drug resistant, relapsed disease.

Project Goal:

In piloting this approach, we identified mutations associated with drug resistance that are present in small numbers even prior to starting therapy. These include mutations in RAS— the second most commonly mutated gene in pediatric AML. We will continue to look at pediatric leukemia to define changes leading to therapy resistance and relapse. We will then look more specifically at how FLT3 and RAS work together to cause treatment resistance. In this way, we will define the genetics of relapse in pediatric AML and contribute a molecular understanding of drug resistance. Ultimately, this will suggest therapies most likely to cure children with an otherwise dismal prognosis.