Protein & Cell

, Volume 1, Issue 2, pp 124–132 | Cite as

Molecular and cellular bases of chronic myeloid leukemia

Review

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the overproduction of granulocytes, which leads to high white blood cell counts and splenomegaly in patients. Based on clinical symptoms and laboratory findings, CML is classified into three clinical phases, often starting with a chronic phase, progressing to an accelerated phase and ultimately ending in a terminal phase called blast crisis. Blast crisis phase of CML is clinically similar to an acute leukemia; in particular, B-cell acute lymphoblastic leukemia (B-ALL) is a severe form of acute leukemia in blast crisis, and there is no effective therapy for it yet. CML is induced by the BCR-ABL oncogene, whose gene product is a BCR-ABL tyrosine kinase. Currently, inhibition of BCR-ABL kinase activity by its kinase inhibitor such as imatinib mesylate (Gleevec) is a major therapeutic strategy for CML. However, the inability of BCR-ABL kinase inhibitors to completely kill leukemia stem cells (LSCs) indicates that these kinase inhibitors are unlikely to cure CML. In addition, drug resistance due to the development of BCRABL mutations occurs before and during treatment of CML with kinase inhibitors. A critical issue to resolve this problem is to fully understand the biology of LSCs, and to identify key genes that play significant roles in survival and self-renewal of LSCs. In this review, we will focus on LSCs in CML by summarizing and discussing available experimental results, including the original studies from our own laboratory.

Keywords

BCR-ABL leukemic stem cells CML therapeutic agents 

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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Yaoyu Chen
    • 1
  • Cong Peng
    • 1
  • Dongguang Li
    • 2
  • Shaoguang Li
    • 1
  1. 1.Division of Hematology/Oncology, Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.School of Computer and Security ScienceEdith Cowan UniversityMount LawleyAustralia

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