
Edward Kaverlerchik, MD
University of California, San Diego
2009
$
50000
Tower Career Development Grant
Targeting CML Stem Cells with a Small Molecule Wnt-Signaling Inhibitor
Hematopoietic stem cells (HSC) are responsible for life-long blood production. When HSC acquires chromosomal derangement BCR-ABL their capacity to become diverse blood cells is altered, leading to expansion of white blood cells causing chronic myeloid leukemia (CML). BCR-ABL inhibition with oral drugs can hold the disease. Many patients demonstrate BCR-ABL resistance that leads to acquisition of new mutations in the HSC daughter cells and progression to acute leukemia stages – the Blast Crisis. Activation of Wnt-signaling pathway is critical for progression. We will test novel small-molecule Wnt-signaling inhibitor MCC-301 and analogs for their capacity to kill BC CML cells.
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