Targeted therapy of chronic myeloid leukemia.

Abstract

Inhibition of BCR-ABL with kinase inhibitors has become a well-accepted strategy for targeted therapy of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML) and has been shown to be highly effective in controlling the disease. However, BCR-ABL kinase inhibitors do not efficiently kill leukemic stem cells (LSCs), indicating that this therapeutic strategy does not lead to a cure of CML. Development of curative therapies of CML require the identification of genes/pathways that play critical roles in survival and self-renewal of LSCs. Targeting of these key BCR-ABL downstream genes provides an opportunity to eradicate LSCs, as shown in our work that identifies the Alox5 gene as a key regulator of the function of CML LSCs. Immediate clinical trials are necessary to test the effectiveness of targeting a key BCR-ABL downstream gene in eradicating LSCs in CML patients. In this review, we will discuss current targeted therapies of CML using BCR-ABL kinase inhibitors, with a focus on the importance of developing a targeted therapy of CML through identification of target genes in CML LSCs.

• Authors: Con Sullivan, Cong Peng, Yaoyu Chen, Dongguang Li, Shaoguang Li
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 80 Issue 5 Pg. 584-91 (Sep 01 2010) ISSN: 1873-2968 [Electronic] England
• PMID: 20470758 (Publication Type: Journal Article, Review)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Disease Models, Animal
• Genes, abl
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, enzymology, genetics)
• Mice