title: Extent of hematopoietic involvement by TET2 mutations in JAK2V⁶¹⁷F polycythemia vera.
abstract: TET2 mutations are found in polycythemia vera and it was initially reported that there is a greater TET2 mutational burden than JAK2(V617F) in polycythemia vera stem cells and that TET2 mutations precede JAK2(V617F). We quantified the proportion of TET2, JAK2(V617F) mutations and X-chromosome allelic usage in polycythemia vera cells, BFU-Es and in vitro expanded erythroid progenitors and found clonal reticulocytes, granulocytes, platelets and CD34(+) cells. We found that TET2 mutations may also follow rather than precede JAK2(V617F) as recently reported by others. Only a fraction of clonal early hematopoietic precursors and largely polyclonal T cells carry the TET2 mutation. We showed that in vitro the concomitant presence of JAK2(V617F) and TET2 mutations favors clonal polycythemia vera erythroid progenitors in contrast with non-TET2 mutated progenitors. We conclude that loss-of-function TET2 mutations are not the polycythemia vera initiating events and that the acquisition of TET2 somatic mutations may increase the aggressivity of the polycythemia vera clone.
authors.affiliation: University of Utah School of Medicine and VAH, Salt Lake City, UT, USA.
authors.forename: Sabina I
authors.initials: SI
authors.lastname: Swierczek
authors.forename: Donghoon
authors.initials: D
authors.lastname: Yoon
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Cécile
authors.initials: C
authors.lastname: Saint-Martin
authors.forename: Francois
authors.initials: F
authors.lastname: Delhommeau
authors.forename: Albert
authors.initials: A
authors.lastname: Najman
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D019943:Amino Acid Substitution; D001792:Blood Platelets / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D041321:Chromosomes, Human, X / Q000235:genetics; D002999:Clone Cells / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism; D006413:Hematopoietic System / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D011087:Polycythemia Vera / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012156:Reticulocytes / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D004921:Erythropoietin; D049308:Dioxygenases; C541081:TET2 protein, human; D053614:Janus Kinase 2