title: Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia.
abstract: 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.
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, United Kingdom. lms52@cam.ac.uk
authors.forename: Linda M
authors.initials: LM
authors.lastname: Scott
authors.forename: Mike A
authors.initials: MA
authors.lastname: Scott
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Green
mesh_terms: 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*
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2