Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia.
An acquired V617F JAK2 mutation occurs in patients with polycythemia vera (PV) or essential thrombocythemia (ET). In a proportion of V617F-positive patients, mitotic recombination produces mutation-homozygous cells that come to predominate with time. However, the prevalence of homozygosity is unclear, as previous reports studied mixed populations of wild-type, V617F-heterozygous, and V617F-homozygous mutant cells. We therefore analyzed 1766 individual hematopoietic colonies from 34 patients with PV or ET in whom granulocyte sequencing demonstrated that the mutant peak did not predominate. V617F-positive erythroid burst-forming units (BFU-Es) were more frequent in patients with PV compared with patients with ET (P = .022) and, strikingly, V617F-homozygous BFU-Es were detected in all 17 patients with PV, but in none of the patients with ET (P < .001). Moreover, mutation-homozygous cells were present in 2 patients with ET after polycythemic transformation. These results demonstrate that V617F-homozygous erythroid progenitors are present in most patients with PV but occur rarely in those with ET.
Scott
Linda M
LM
Department of Haematology, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, United Kingdom. lms52@cam.ac.uk
Scott
Mike A
MA
Campbell
Peter J
PJ
Green
Anthony R
AR
D001483:Base Sequence; D004252:DNA Mutational Analysis; D018450:Disease Progression; D015672:Erythroid Precursor Cells / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2; D008969:Molecular Sequence Data; D017354:Point Mutation; D011087:Polycythemia Vera / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D013920:Thrombocythemia, Essential / Q000235:genetics*
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2