JAK2V617F homozygosity arises commonly and recurrently in PV and ET, but PV is characterized by expansion of a dominant homozygous subclone

被引:78
作者
Godfrey, Anna L. [1 ,2 ,3 ,4 ]
Chen, Edwin [1 ,2 ,4 ]
Pagano, Francesca [1 ,2 ]
Ortmann, Christina A. [1 ,2 ,3 ]
Silber, Yvonne [1 ,2 ]
Bellosillo, Beatriz [5 ]
Guglielmelli, Paola [6 ,7 ]
Harrison, Claire N. [8 ]
Reilly, John T. [9 ]
Stegelmann, Frank [10 ]
Bijou, Fontanet [11 ]
Lippert, Eric [12 ,13 ]
McMullin, Mary F. [14 ]
Boiron, Jean-Michel [15 ]
Doehner, Konstanze [10 ]
Vannucchi, Alessandro M. [7 ]
Besses, Carlos [5 ]
Campbell, Peter J. [16 ]
Green, Anthony R. [1 ,2 ,4 ]
机构
[1] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England
[2] Univ Cambridge, Dept Haematol, Cambridge CB2 0XY, England
[3] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 2QQ, England
[4] Univ Cambridge, Stem Cell Inst, Cambridge, England
[5] Hosp Mar IMIM, Dept Haematol, Barcelona, Spain
[6] Univ Florence, Sect Hematol, Dept Med & Surg Care, Florence, Italy
[7] Ist Toscano Tumori, Florence, Italy
[8] Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England
[9] Royal Hallamshire Hosp, Dept Haematol, Sheffield S10 2JF, S Yorkshire, England
[10] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany
[11] Etab Francais Sang Aquitaine Limousin, Bordeaux, France
[12] Univ Bordeaux Segalen, Ctr Hosp Univ Bordeaux, Hematol Lab, Bordeaux, France
[13] Univ Bordeaux Segalen, Inserm U 1035, Lab Hematopoiese Leucem & Cibles Therapeut, Bordeaux, France
[14] Belfast City Hosp, Dept Haematol, Belfast BT9 7AD, Antrim, North Ireland
[15] Hop Haut Leveque, Dept Haematol, Etab Francais Sang Aquitaine Limousin, Bordeaux, France
[16] Wellcome Trust Sanger Inst, Cambridge, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
JAK2 617V-GREATER-THAN-F MUTATION; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; MYELOPROLIFERATIVE DISORDERS; ALLELE BURDEN; CLONAL ANALYSIS; JAK2-V617F; MYELOFIBROSIS; HETEROGENEITY;
D O I
10.1182/blood-2012-05-431791
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Subclones homozygous for JAK2V617F are more common in polycythemia vera (PV) than essential thrombocythemia (ET), but their prevalence and significance remain unclear. The JAK2 mutation status of 6495 BFU-E, grown in low erythropoietin conditions, was determined in 77 patients with PV or ET. Homozygous-mutant colonies were common in patients with JAK2V617F-positive PV and were surprisingly prevalent in JAK2V617F-positive ET and JAK2 exon 12-mutated PV. Using microsatellite PCR to map loss-of-heterozygosity breakpoints within individual colonies, we demonstrate that recurrent acquisition of JAK2V617F homozygosity occurs frequently in both PV and ET. PV was distinguished from ET by expansion of a dominant homozygous subclone, the selective advantage of which is likely to reflect additional genetic or epigenetic lesions. Our results suggest a model in which development of a dominant JAK2V617F-homzygous subclone drives erythrocytosis in many PV patients, with alternative mechanisms operating in those with small or undetectable homozygous-mutant clones. (Blood. 2012; 120(13):2704-2707)
引用
收藏
页码:2704 / 2707
页数:4
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