Leukemia stem cells in T-ALL

We are continuing our work examining the roles of PKCθ and Wnt signaling, as well as pursuing exciting new leads emanating from our human cord blood model, in establishing/maintaining leukemia stem cell activity in T-ALL.

In the PKCθ project, we have taken a biochemical approach to dissecting downstream pathways. We developed an analog-specific kinase variant of PKCθ, followed by discovery mode mass spectrometry (LC-ESI-MS/MS) to define direct kinase targets, and are pursuing functional validation of hits. This work is being done in collaboration with Gregg Morin at BCCA.

Pathogenetic mechanisms in T-ALL

Using our recently developed cord blood transduction approach, we are able to generate synthetic T-ALL by de novo transformation of normal human hematopoietic progenitors with activated NOTCH1 in combination with accessory oncogenes (M. Kusakabe et al, Nature Communications, 2019). This model generates polyclonal expansions of pre-leukemia cells in vitro within 3-4 weeks, which then produce clonal T-ALL disease within 3 months after injection into immunodeficient mice. Using this model, we are actively exploring the following areas:

Leukemia and Myeloma Program (LaMP)

Leukemia and Myeloma Program (LaMP) is a bench-to-bedside-and-back research network creating a seamless continuum of fundamental science to clinical care. It’s a new effort that has evolved from a 40-year history of collaborative research in BC focused on developing the knowledge required to make improvements in the long-term outcomes of patients with leukemia and multiple myeloma.
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