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
. 2021 Apr;35(2):205-216.
doi: 10.1016/j.hoc.2020.11.003. Epub 2020 Dec 9.

The Microenvironment in Myeloproliferative Neoplasms

Gajalakshmi Ramanathan  1 , Angela G Fleischman  2
Affiliations
Review

The Microenvironment in Myeloproliferative Neoplasms

Gajalakshmi Ramanathan et al. Hematol Oncol Clin North Am. 2021 Apr.

Abstract

Chronic inflammation is a hallmark of myeloproliferative neoplasms (MPNs), with elevated levels of proinflammatory cytokines being commonly found in all 3 subtypes. Systemic inflammation is responsible for the constitutional symptoms, thrombosis risk, premature atherosclerosis, and disease evolution in MPN. Although the neoplastic clone and their differentiated progeny drive the inflammatory process, they also induce ancillary cytokine secretion from nonmalignant cells. Here, the authors describe the inflammatory milieu in MPN based on soluble factors and cellular mediators. They also discuss the prognostic value of cytokine measurements in patients with MPN and potential therapeutic strategies that target the cellular players in inflammation.

Keywords: Cytokines; Inflammation; Microenvironment; Myeloid cells; Myeloproliferative neoplasm; Prognosis.

PubMed Disclaimer

Conflict of interest statement

Disclosures The authors declare that they have no conflict of interests. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number T32CA009054. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

Figure 1.
Figure 1.
MPN-associated cytokines and chemokines according to subtype. Dkk-1, Dickkopf-related protein 1; EGF, epidermal growth factor; GRO-a, growth-regulated oncogene; HGF, hepatocyte growth factor; IFNa, interferon alpha; IFNg, interferon gamma; IL-1RA, interleukin-1 receptor antagonist; IP-10, IFN-g–inducible protein 10; MIG, monokine induced by IFN-gamma; MIP, macrophage inflammatory protein-1; TGF-a, transforming growth factor alpha; TNFa, tumor necrosis factor alpha.
Figure 2.
Figure 2.
Overview of the inflammatory loop in MPNs. The neoplastic hematopoietic stem cell (HSC) clone carrying the JAK2V617F, CALR, or MPL, mutation secretes cytokines involved in inflammation and differentiate into malignant cells of the myeloid lineage such as megakaryocytes, monocytes, and granulocytes. Together, these cells produce a host of cytokines creating an inflammatory microenvironment which in turn results in aberrant activation and function of non-malignant cells in the bone marrow and peripheral blood. NETs, neutrophil extracellular traps; MSC, mesenchymal stromal cell; vWF, von Willebrand factor; PLAs, platelet-leukocyte aggregates.
See this image and copyright information in PMC

References

    1. Reikvam H, Fredly H, Kittang AO, Bruserud O. The possible diagnostic and prognostic use of systemic chemokine profiles in clinical medicine—the experience in acute myeloid leukemia from disease development and diagnosis via conventional chemotherapy to allogeneic stem cell transplantation. Toxins (Basel). Feb 2013;5(2):336–62. doi:10.3390/toxins5020336 - DOI - PMC - PubMed
    1. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. Apr 2005;7(4):387–97. doi:10.1016/j.ccr.2005.03.023 - DOI - PubMed
    1. James C, Ugo V, Le Couédic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. Apr 2005;434(7037):1144–8. doi:10.1038/nature03546 - DOI - PubMed
    1. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. Apr 2005;352(17):1779–90. doi:10.1056/NEJMoa051113 - DOI - PubMed
    1. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar 19–25 2005;365(9464):1054–61. doi:10.1016/S0140-6736(05)71142-9 - DOI - PubMed

Publication types