Details

Autor(en) / Beteiligte

• Godfrey, Anna L.
• Chen, Edwin
• Pagano, Francesca
• Ortmann, Christina A.
• Silber, Yvonne
• Bellosillo, Beatriz
• Guglielmelli, Paola
• Harrison, Claire N.
• Reilly, John T.
• Stegelmann, Frank
• Bijou, Fontanet
• Lippert, Eric
• McMullin, Mary F.
• Boiron, Jean-Michel
• Döhner, Konstanze
• Vannucchi, Alessandro M.
• Besses, Carlos
• Campbell, Peter J.
• Green, Anthony R.

Titel

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

Ist Teil von

• Blood, 2012-09, Vol.120 (13), p.2704-2707

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.