A role of NF-E2 in chronic inflammation and clonal evolution in essential thrombocythemia, polycythemia vera and myelofibrosis?

Leuk Res. 2014 Feb;38(2):263-6. doi: 10.1016/j.leukres.2013.07.002. Epub 2013 Aug 9.

Abstract

A novel murine model for myeloproliferative neoplasms (MPNs) generated by overexpression of the transcription factor NF-E2 has recently been described. Sustained overexpression of NF-E2 in this model induced myeloid expansion with anemia, leukocytosis and thrombocytosis. Herein, it is debated if NF-E2 overexpression also might have induced a sustained state of in vivo leukocyte and platelet activation with chronic and self-perpetuating production of inflammatory products from activated leukocytes and platelets. If so, this novel murine model also may excellently describe the deleterious impact of sustained chronic NF-E2 overexpression during uncontrolled chronic inflammation upon the hematopoietic system--the development of clonal myeloproliferation. Accordingly, this novel murine model may also have delivered the proof of concept of chronic inflammation as a trigger and driver of clonal evolution in MPNs.

Keywords: Chronic inflammation; Experimental inflammation model; Human inflammation model; IL-1beta; IL-6; IL-8; Myeloproliferative neoplasms; NF-E2 overexpression; NF-kappabeta activation; Reactive oxygen species (ROS); TNF-alpha.

MeSH terms

  • Animals
  • Chronic Disease
  • Clonal Evolution / genetics*
  • Disease Models, Animal
  • Humans
  • Inflammation / genetics*
  • Mice
  • NF-E2 Transcription Factor, p45 Subunit / physiology*
  • Polycythemia Vera / genetics*
  • Primary Myelofibrosis / genetics*
  • Thrombocythemia, Essential / genetics*

Substances

  • NF-E2 Transcription Factor, p45 Subunit
  • Nfe2 protein, mouse