Abstrakt

Targeting chronic myeloid leukemia stem cells

Shaoguang Li

Cancer stem cells in many hematologic malignancies and some solid tumors are associated with cancer initiation and insensitivity to chemotherapy and need to be eradicated for achieving a cure. A successful cancer therapy relies on targeting critical signaling genes that play a key role in the maintenance of cancer stem cell survive and proliferation. Hence, it will be vital to fully apprehend the molecular mechanisms by which cancer stem cells survival and proliferate. Toward this goal, a physiological cancer stem cell disease model is required for identifying and testing genes/pathways that play an essential role in functional regulation of cancer stem cells and can be targeted for eradicating these stem cells. Human continual myeloid leukemia (CML) triggered by way of the BCR-ABL oncogene is derived from a stem cell, serving as a good disease model for studying the molecular biology of cancer stem cells. In CML, BCR-ABL tyrosine kinase inhibitors including imatinib mesylate (Gleevec) are fairly effective in controlling continual section CML, but they fail to eliminate leukemia-starting up cells or leukemia stem cells (LSCs) in CML mice and patients. Clinically, an entire and sustained molecular remission (undetectable stages of BCR-ABL transcripts) is difficult to gain even after an entire cytogenetic remission achieved thru imatinib treatment. It has emerge as clean that BCR-ABL kinase inhibitors can efficiently kill exceptionally proliferating leukemia cells but are incapable of eradicating LSCs for cure. An anti-LSC strategy needs to be developed. Our laboratory has been focusing on know-how the biology of LSCs in CML to identify key genes that modify survival and proliferation of LSCs, assisting us to expand new therapeutic techniques via targeting LSCs.