A role of NF-E2 in chronic inflammation and clonal evolution in essential thrombocythemia, polycythemia vera and myelofibrosis?
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.
Department of Hematology, Roskilde Hospital, University of Copenhagen, Denmark. Electronic address: hans.hasselbalch@dadlnet.dk.
Hans C
HC
Hasselbalch
D000818:Animals; D002908:Chronic Disease; D060965:Clonal Evolution / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D051379:Mice; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000502:physiology*; D011087:Polycythemia Vera / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics*
D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse
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