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

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Godfrey AL,Chen E,Pagano F,Ortmann CA,Silber Y,Bellosillo B,Guglielmelli P,Harrison CN,Reilly JT,Stegelmann F,Bijou F,Lippert E,McMullin MF,Boiron JM,Döhner K,Vannucchi AM,Besses C,Campbell PJ,Green AR

doi

10.1182/blood-2012-05-431791

subject

Has Abstract

pub_date

2012-09-27 00:00:00

pages

2704-7

issue

13

eissn

0006-4971

issn

1528-0020

pii

blood-2012-05-431791

journal_volume

120

pub_type

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