Targeting Leukemia Stem Cells with Novel Therapeutic Agents
Pp. 397-409 (13)
Yaoyu Chen, Cong Peng, Dongguang Li and Shaoguang Li
Chronic myeloid leukemia (CML) is induced by the BCR-ABL oncogene, a
product of Philadelphia (Ph) chromosome. The BCR-ABL kinase inhibitor imatinib is a
standard treatment for Ph+ leukemia, and has been shown to induce a complete
hematologic and cytogenetic response in most chronic phrase CML patients. However,
imatinib does not cure CML, and one of the reasons is that imatinib does not kill
leukemia stem cells (LSCs) in CML both in vitro and in vivo. Recently, several new
targets or drugs have been reported to inhibit LSCs in cultured human CD34+ CML
cells or in mouse model of BCR-ABL induced CML, including an Alox5 pathway
inhibitor, Hsp90 inhibitors, omacetaxine, hedgehog inhibitor and BMS-214662.
Specific targeting of LSCs but not normal stem cell is a correct strategy for developing
new anti-cancer therapies in the future.
Chronic myeloid leukemia (CML), BCR-ABL oncogene, Philadelphia
(Ph) chromosome, BCR-ABL kinase inhibitor, leukemia stem cells (LSCs), Hsp90
inhibitors, omacetaxine, hedgehog inhibitor, BMS-214662, Alox5 inhibitor.
University of Massachusetts Medical School, Department of Medicine, 364 Plantation Street, Worcester, MA 01605, USA