Childhood Cancer

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Elucidating the Roles of Aneuploidy in Down Syndrome-Associated Leukemia

Boston Children’s Hospital
Chun-Chin Chen, PhD
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Leukemia, Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL)
Project Description: 

Down syndrome is one of the most common genetic disorders worldwide. It affects a relatively high proportion of newborns every year - about 1 out of every 700 babies has Down syndrome in the US according to CDC. This condition causes a spectrum of developmental issues that affect the quality of life of these children. Notably, children with Down syndrome are highly prone to blood disorders and childhood leukemia. They have an approximately 20-fold increase in the risk of overall leukemia, particularly acute myeloid leukemia and acute lymphoblastic leukemia. These children also have lower tolerance to chemotherapies due to complications, creating a complex situation for treatments of leukemia. Thus, a deeper understanding of the mechanisms of Down syndrome-associated leukemia can help improve therapeutic interventions, which will be extremely beneficial for this group of children.

Project Goal:

To this day, it remains an open question as to why blood cancers develop so frequently in children with Down syndrome and why these children are particularly sensitive to chemotherapies. The goal of this study is to understand the mechanisms that make children with Down syndrome highly vulnerable to leukemia development. We propose that the cause of Down syndrome-associated leukemia is related to the abnormal genetic background that induces systemic stress in the homeostatic functions of blood stem cells, leading to changes in the property of these cells and leukemia initiation. We will use a range of advanced genomic and genetic approaches to study Down syndrome-associated leukemia both in tissue culture and in animal models. It is our anticipation that the identification of novel mechanisms from this study can help explain why children with Down syndrome are prone to blood cancers. Importantly, we envision that understanding these mechanisms will enable the discovery of more effective therapeutic options that can lower the doses of chemotherapies and reduce treatment-related complications in children with Down syndrome-associated leukemia.