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Roles of JAK2 in Aging, Inflammation, Hematopoiesis and Malignant Transformation

1
Innere Medizin 2, Hämatologie und Onkologie, Universitätsklinikum Jena, 07747 Jena, Germany
2
Leibniz-Institute on Aging–Fritz Lipmann Institute (FLI), 07745 Jena, Germany
3
Dana-Farber Cancer Institute, Department of Pediatric Oncology, Harvard University, Boston, MA 02467, USA
4
Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02129, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 854; https://doi.org/10.3390/cells8080854
Received: 9 July 2019 / Revised: 5 August 2019 / Accepted: 6 August 2019 / Published: 8 August 2019
(This article belongs to the Special Issue Aging and Regeneration)
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PDF [8491 KB, uploaded 16 August 2019]
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Abstract

Clonal alterations in hematopoietic cells occur during aging and are often associated with the establishment of a subclinical inflammatory environment. Several age-related conditions and diseases may be initiated or promoted by these alterations. JAK2 mutations are among the most frequently mutated genes in blood cells during aging. The most common mutation within the JAK2 gene is JAK2-V617F that leads to constitutive activation of the kinase and thereby aberrant engagement of downstream signaling pathways. JAK2 mutations can act as central drivers of myeloproliferative neoplasia, a pre-leukemic and age-related malignancy. Likewise, hyperactive JAK-signaling is a hallmark of immune diseases and critically influences inflammation, coagulation and thrombosis. In this review we aim to summarize the current knowledge on JAK2 in clonal hematopoiesis during aging, the role of JAK-signaling in inflammation and lymphocyte biology and JAK2 function in age-related diseases and malignant transformation. View Full-Text
Keywords: JAK2; Janus-kinase; aging; clonal hematopoiesis (CHIP), myeloproliferative neoplasia (MPN) JAK2; Janus-kinase; aging; clonal hematopoiesis (CHIP), myeloproliferative neoplasia (MPN)
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Perner, F.; Perner, C.; Ernst, T.; Heidel, F.H. Roles of JAK2 in Aging, Inflammation, Hematopoiesis and Malignant Transformation. Cells 2019, 8, 854.

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