|Title||JAK2V617F homozygosity arises commonly and recurrently in PV and ET, but PV is characterized by expansion of a dominant homozygous subclone|
|Authors||Godfrey, A.L., Chen, E., Pagano, F., Ortmann, C.A., Silber, Y., Belosillo, B., Guglielmelli, P., Harrison, C., Reilly, J.T., Stegelmann, F., Bijou, F., Lippert, E., McMullin, M.F., Boiron, J.M., Doehner, K., Vannucchi, A.M., Besses, C., Campbell, P.J. and Green, A.R.|
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 citation||120, pp. 2704-2707|
|Publisher||American Society of Hematology|
|Digital Object Identifier (DOI)||https://doi.org/10.1182/blood-2012-05-431791|
|Published||27 Dec 2012|