Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia

• Published in: Blood 2006-10, Vol.108 (7), p.2435-2437
• Main Authors: Scott, Linda M., Scott, Mike A., Campbell, Peter J., Green, Anthony R.
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Disease Progression; DNA Mutational Analysis; Erythroid Precursor Cells - metabolism; Granulocytes - cytology; Hematologic and hematopoietic diseases; Heterozygote; Homozygote; Humans; Janus Kinase 2; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Molecular Sequence Data; Point Mutation; Polycythemia Vera - genetics; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - physiology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Stem Cells - cytology; Thrombocythemia, Essential - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-04-018259

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.