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Exp Hematol. 2016 Jan;44(1):24-9.e1. doi: 10.1016/j.exphem.2015.09.006. Epub 2015 Oct 13.

JAK2(V617I) results in cytokine hypersensitivity without causing an overt myeloproliferative disorder in a mouse transduction-transplantation model.

Author information

1
Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA.
2
Knight Cancer Institute, Oregon Health & Science University, Portland, OR.
3
Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA. Electronic address: agf@uci.edu.

Abstract

A germline JAK2(V617I) point mutation results in hereditary thrombocytosis and shares some phenotypic features with myeloproliferative neoplasm, a hematologic malignancy associated with a somatically acquired JAK2(V617F) mutation. We established a mouse transduction-transplantation model of JAK2(V617I) that recapitulated the phenotype of humans with germline JAK2(V617I). We directly compared the phenotypes of JAK2(V617I) and JAK2(V617F) mice. The JAK2(V617I) mice had increased marrow cellularity with expanded myeloid progenitor and megakaryocyte populations, but this phenotype was less severe than that of JAK2(V617F) mice. JAK2(V617I) resulted in cytokine hyperresponsiveness without constitutive activation in the absence of ligand, whereas JAK2(V617F) resulted in constitutive activation. This may explain why JAK2(V617I) produces a mild myeloproliferative phenotype in the mouse model, as well as in humans with germline JAK2(V617I) mutations.

PMID:
26458983
PMCID:
PMC5685804
DOI:
10.1016/j.exphem.2015.09.006
[Indexed for MEDLINE]
Free PMC Article

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