Hematopoietic stem cells, progenitor cells and leukemic stem cells in adult myeloproliferative neoplasms

Abstract

The understanding of myeloproliferative neoplasms has changed dramatically since Dameshek proposed his classification over 50 years ago. Our knowledge of the types of cells which constitute the hematopoietic system and of how they are regulated has also appreciated significantly over this time. This review relates what is currently known about the acquired genetic mutations associated with adult myeloproliferative neoplasms to how they lead to the hematopoietic perturbations of myeloproliferative disease. There is a particular focus on how stem and progenitor cell compartments are affected by BCR–ABL1 and JAK2V617F mutations, and the particular issue of resistance of leukemic stem cells to conventional and targeted therapies.

Keywords::

• Myeloproliferative neoplasms
• stem and primitive progenitor cells
• signal transduction

Acknowledgements

The author's studies are supported by Australian National Heath and Medical Research Council Program Grant 461219; Independent Research Institutes Infrastructure Support Scheme; Cure Cancer Australia/Leukaemia Foundation Australia Post Doctoral Fellowship; Lion's Fellowship, Cancer Council of Victoria; the Australian Cancer Research Fund; and a grant from the Victorian State Government Operational Infrastructure Support.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.