Progenitor profiling for preleukemia diagnosis, leukemia clinical staging, and prognosis of disease progression

Stanford researchers have identified methods to phenotype and stage leukemic conditions by differential analysis of the distribution of hematopoietic stem and progenitor cell subsets in clinical hematological samples. These methods represent a useful tool to diagnose preleukemia, prognose disease progression and monitor therapeutic success of the chosen cancer treatment. This disclosure also includes methods to identify leukemia stem cells, which are involved in disease progression and development of resistance to chemotherapeutic drugs. Unlike typical hematopoietic progenitor cells, leukemia stem cells have activated the beta-catenin pathway and, as a result, behave like hematopoietic stem cells, in that they acquire the capacity to self-renew and, thus, to facilitate the long-term proliferation of the cancer. The proliferation of leukemia stem cells can be blocked by inhibitors of the Wnt/beta-catenin pathway. This process can be monitored both in vitro using replating assays and in vivo using bioluminescent imaging of transplanted leukemia stem cell populations in a highly immunocompromised mouse model. It is critical to determine the efficacy of a chemotherapeutic agent or regimen in eliminating these self-renewing leukemia stem cells by monitoring the proliferation and self-renewal of leukemia stem cells. The technology described may have broader applications in the detection and elimination of cancer stem cells in other malignancies that have activated the Wnt/beta-catenin pathway such as colon, hepatocellular and breast cancer.