Identify Novel Druggable Targets to Treat Philadelphia chromosome-like B-Acute Lymphoblastic Leukemia
B cell - Acute lymphoblastic leukemia (B-ALL) is the leading cause of cancer-related death in children and adolescence, 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, as well as mutations in genes that control normal B cell differentiation. Disruption in these key pathways confers uncontrolled proliferation of poorly differentiated B cells, ultimately leads to full-blown leukemias that can be resistant to conventional therapies.
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.