Send to

Choose Destination
See comment in PubMed Commons below
Leuk Res. 2011 Oct;35(10):1279-85. doi: 10.1016/j.leukres.2011.05.037. Epub 2011 Jul 1.

The two faces of myeloproliferative neoplasms: Molecular events underlying lymphoid transformation.

Author information

Department of Haematology, Imperial College, Du Cane Road, London W12 0HS, UK.


Multipotent haematopoietic stem cells pass through stages of differentiation with the progressive loss of developmental options leading to the production of terminally differentiated mature blood cells. This process is regulated by soluble cytokines binding to a ligand specific cell surface receptor on a precursor cell. Key to signal transduction are tyrosine kinase proteins which can be divided into two sub families, the receptor protein tyrosine kinases which are transmembrane receptors and retain an intact catalytic kinase domain and the cytoplasmic tyrosine kinases which bind to cytokine receptors. Abnormalities of tyrosine kinase proteins are well recognised in myeloid malignancies, mutation in the cytoplasmic tyrosine kinase JAK2 (V617F) is key in the pathogenesis of myeloproliferative neoplasms, and translocations involving ABL key in the development of chronic myeloid leukaemia. However tyrosine kinase mutations are increasingly recognised to play a role in the pathogenesis of a wider range of haematological cancers. This review focuses on the role of deregulated tyrosine kinase genes either as part of novel fusion proteins involving FGFR1, PDGFRα, PDGFRβ, JAK2 and ABL, or as a consequence of point mutation in JAK1 or JAK2 in the development of precursor T and B lymphoid malignancies or mixed myeloid/lymphoid disorders. We also set out some of the postulated mechanisms which underlie the association of tyrosine kinase mutations with the development of lymphoid malignancy.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center