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JAK2 and genomic instability in the myeloproliferative neoplasms: A case of the chicken or the egg?
Author(s) -
Scott Linda M.,
Rebel Vivienne I.
Publication year - 2012
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23243
Subject(s) - genome instability , janus kinase 2 , cancer research , mutation , haematopoiesis , biology , myeloproliferative disorders , myeloid , intracellular , stem cell , genetics , signal transduction , dna damage , immunology , dna , gene
Abstract The myeloproliferative neoplasms (MPNs) are a particularly useful model for studying mutation accumulation in neoplastic cells, and the mechanisms underlying their acquisition. This review summarizes our current understanding of the molecular defects present in patients with an MPN, and the effects of mutations targeting Janus kinase 2 (JAK2)‐mediated intracellular signaling on DNA damage and on the elimination of mutation‐bearing cells by programmed cell death. Moreover, we discuss findings that suggest that the acquisition of disease‐initiating mutations in hematopoietic stem cells of some MPN patients may be the consequence of an inherent genomic instability that was not previously appreciated. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.