Childhood Cancer

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Identify Novel Druggable Targets to Treat Philadelphia chromosome-like B-Acute Lymphoblastic Leukemia

Children's Hospital of Philadelphia
Wei Tong, PhD
Grant Type: 
Innovation Grants
Year Awarded: 
Type of Childhood Cancer: 
Leukemia, Acute Lymphoblastic Leukemia (ALL)
Project Description: 

Acute lymphoblastic leukemia (ALL) is the leading cause of cancer-related death in young people, and commonly has a poor outcome in adults. The high-risk ALL is a subtype of ALL that fare a high rate of relapse and mortality. Intriguingly, high-risk ALLs show increased signaling response to growth factors that results in uncontrolled cell proliferation. This study focuses on a critical regulator of growth factor signaling pathway and also a novel tumor suppressor, to improve our understanding of the pathogenesis of childhood leukemias. In the past year, we made significant progress in understanding how this signaling pathway works in animal models of ALL. We dissected the developmental stages and signaling pathways of the B cell progenitors that are affected by the genes dysregulated in human B-ALLs. Moreover, we revealed strategies to target leukemic cells through our mechanistic studies. We will continue screening for new therapeutic relevant target in our mouse models in vivo which may enable us to overcome drug resistance or improve conventional therapies.

Project Goal

This study focuses on dissecting how different key pathways, when mutated, act together to promote B-ALL initiation, progression, and therapy resistance. Furthermore, this study proposes to use novel mouse models to screen for novel druggable targets that abrogate B-ALL development in its native environment in mice, a cell-cell context that cannot be faithfully recapitulated in cell cultures. Therefore, our proposed research will likely improve our understanding of the pathogenesis of childhood leukemias, and reveal strategies to target leukemic cells that are resistant to current therapies.