Extent of hematopoietic involvement by TET2 mutations in JAK2V617F polycythemia vera

Extent of hematopoietic involvement by TET2 mutations in JAK2V617F polycythemia vera

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TET2 mutations are found in polycythemia vera and it was initially reported that there is a greater TET2 mutational burden than JAK2V617F in polycythemia vera NEROLI OIL stem cells and that TET2 mutations precede JAK2V617F.We quantified the proportion of TET2, JAK2V617F 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 Oven Control Knob precede JAK2V617F 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 JAK2V617F 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.