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

Blood - Tập 108 - Trang 2435-2437 - 2006
Linda M. Scott, Mike A. Scott, Peter J. Campbell, Anthony R. Green

Tóm tắt

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.

Tài liệu tham khảo

Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365: 1054-1061. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7: 387-397. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434: 1144-1148. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352: 1779-1790. Zhao R, Xing S, Li Z, et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem. 2005;280: 22788-22792. Campbell PJ, Scott LM, Buck G, et al. Definition of sub-types of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet. 2005;366: 1945-1953. Kralovics R, Guan Y, Prchal JT. Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera. Exp Hematol. 2002;30: 229-236. Lasho TL, Mesa R, Gilliland DG, Tefferi A. Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2 (V617F) in granulocytes. Br J Haematol. 2005;130: 797-799. Tefferi A, Sirhan S, Lasho TL, et al. Concomitant neutrophil JAK2 mutation screening and PRV-1 expression analysis in myeloproliferative disorders and secondary polycythaemia. Br J Haematol. 2005;131: 166-171. Tefferi A, Lasho TL, Schwager SM, et al. The JAK2 (V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol. 2005;131: 320-328. Pearson TC. Evaluation of diagnostic criteria in polycythemia vera. Semin Hematol. 2001;38: 21-24. Murphy S, Peterson P, Iland H, Laszlo J. Experience of the polycythemia vera study group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Semin Hematol. 1997;34: 29-39. Campbell PJ, Scott LM, Baxter EJ, Bench AJ, Green AR, Erber WN. Methods for the detection of the JAK2 V617F mutation in human myeloproliferative disorders. In: Iland H, Hertzberg M, Marlton P, eds. Myeloid Leukemia: Methods and Protocols: Methods in Molecular Medicine. Vol. 125 Totowa, NJ: Humana Press; 2005: 253-264. Landschulz KT, Noyes AN, Rogers O, Boyer SH. Erythropoietin receptors on murine erythroid colony-forming units: natural history. Blood. 1989;73: 1476-1486. Shih LY, Lee CT. Identification of masked polycythemia vera from patients with idiopathic marked thrombocytosis by endogenous erythroid colony assay. Blood. 1994;83: 744-748. Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353: 33-45.