Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Aug 8;8(8):854.
doi: 10.3390/cells8080854.

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

Florian Perner  1   2   3 , Caroline Perner  4 , Thomas Ernst  1 , Florian H Heidel  5   6
Affiliations
Review

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

Florian Perner et al. Cells. .

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.

Keywords: JAK2; Janus-kinase; aging; clonal hematopoiesis (CHIP), myeloproliferative neoplasia (MPN).

PubMed Disclaimer

Conflict of interest statement

F.H.H. has served as an advisory board member for Novartis, CTI and Celgene and has received research funding from Novartis.

Figures

Figure 1
Figure 1
Schematic of clonal development in hematopoietic stem and progenitor cells during aging. Representative example of the sequence of TET2 loss of function (LOF), Janus Kinase 2 (JAK2-V617F) and Nucleophosmin (NPM1c) mutations leading to clonal hematopoiesis, a myeloproliferative neoplasia (MPN) and finally to the development of acute myeloid leukemia (AML) respectively.
Figure 2
Figure 2
Schematic representation of normal and aberrant JAK-signal transduction. The IL2-receptor (IL2-R) associated with JAK1 and JAK3 serves in this cartoon as an example for physiological JAK-signaling dependent on cytokine binding. JAK2-V617F (JAK2-VF) is representatively depicted in association with the Erythropoetin-receptor (EPO-R) and the Thrombopoetin-receptor (TPO-R) where it induces constitutive activation and ligand hypersensitivity, respectively.
See this image and copyright information in PMC

References

    1. Beerman I., Bhattacharya D., Zandi S., Sigvardsson M., Weissman I.L., Bryder D., Rossi D.J. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc. Natl. Acad. Sci. USA. 2010;107:5465–5470. doi: 10.1073/pnas.1000834107. - DOI - PMC - PubMed
    1. Dykstra B., Olthof S., Schreuder J., Ritsema M., de Haan G. Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J. Exp. Med. 2011;208:2691–2703. doi: 10.1084/jem.20111490. - DOI - PMC - PubMed
    1. Busque L., Mio R., Mattioli J., Brais E., Blais N., Lalonde Y., Maragh M., Gilliland D.G. Nonrandom X-inactivation patterns in normal females: Lyonization ratios vary with age. Blood. 1996;88:59–65. - PubMed
    1. Gale R.E., Wheadon H., Boulos P., Linch D.C. Tissue specificity of X-chromosome inactivation patterns. Blood. 1994;83:2899–2905. - PubMed
    1. Busque L., Patel J.P., Figueroa M.E., Vasanthakumar A., Provost S., Hamilou Z., Mollica L., Li J., Viale A., Heguy A., et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat. Genet. 2012;44:1179–1181. doi: 10.1038/ng.2413. - DOI - PMC - PubMed

Publication types