Current Hematologic Malignancy Reports

, Volume 6, Issue 2, pp 82–87

In Search of CML Stem Cells’ Deadly Weakness

  • Francesca Pellicano
  • Amy Sinclair
  • Tessa L. Holyoake
Article

DOI: 10.1007/s11899-011-0085-y

Cite this article as:
Pellicano, F., Sinclair, A. & Holyoake, T.L. Curr Hematol Malig Rep (2011) 6: 82. doi:10.1007/s11899-011-0085-y
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Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that is characterized by the presence of a fusion oncogene, BCR-ABL, which encodes a protein with constitutive tyrosine kinase activity. This activity causes excessive production of myeloid cells and their premature release into the circulation. The discovery of tyrosine kinase inhibitors marked a major advance in CML therapy, but these drugs cannot eradicate the disease because they are unable to kill the most primitive, quiescent leukemic stem cells. This review discusses current research in CML and attractive targets that have emerged with potential for eradicating the disease. Several new targets have recently been investigated as potential modulators in myeloid leukemia pathogenesis, including the multiple gene regulators miRNAs, the apparently leukemia-specific cell surface marker IL1RAP, transcription factors such as BMI1 and FOXOs, the tumor suppressors PML and PP2A, and the tyrosine kinase JAK2.

Keywords

Chronic myeloid leukemia BCR-ABL Tyrosine kinase inhibitors TKIs Haematopoietic stem cells HSC Quiescence CD34+ CD38- cells Philadelphia chromosome FOXOs PML IL1RAP Immune therapy BMI1 JAK2 PP2A MicroRNA miR-203 miR-328 TGF-β. 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Francesca Pellicano
    • 1
  • Amy Sinclair
    • 1
  • Tessa L. Holyoake
    • 1
  1. 1.Paul O’Gorman Leukaemia Research Centre, Institute for Cancer SciencesUniversity of GlasgowGlasgowUK

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