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Extent of hematopoietic involvement by TET2 mutations in JAK2V⁶¹⁷F polycythemia vera

Haematologica. 2011 May;96(5):775-8. doi: 10.3324/haematol.2010.029678. Epub 2011 Jan 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Blood Platelets / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chromosomes, Human, X / genetics
  • Clone Cells / metabolism
  • DNA-Binding Proteins / genetics*
  • Dioxygenases
  • Erythroid Precursor Cells / metabolism
  • Erythropoietin / pharmacology
  • Female
  • Flow Cytometry
  • Granulocytes / metabolism
  • Hematopoietic System / metabolism
  • Humans
  • Janus Kinase 2 / genetics*
  • Mutation*
  • Polycythemia Vera / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Reticulocytes / metabolism
  • T-Lymphocytes / metabolism
  • Time Factors

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Erythropoietin
  • Dioxygenases
  • TET2 protein, human
  • Janus Kinase 2