JAK2 and genomic instability in the myeloproliferative neoplasms: a case of the chicken or the egg?
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.
Greehey Children's Cancer Research Institute, University of Texas Health Sciences Center at San Antonio, San Antonio, TX 78229, USA. linda.scott8007@gmail.com
Linda M
LM
Scott
Vivienne I
VI
Rebel
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004249:DNA Damage; D042822:Genomic Instability; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011087:Polycythemia Vera / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D055728:Primary Myelofibrosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000201:enzymology / Q000235:genetics
D053614:Janus Kinase 2