Proteomic study of the impact of the JAK2-V617F mutation on the phenotype of essential thrombocythemia.

Objective: Previous studies have suggested that two subtypes of essential thrombocythemia (ET) could be separated on the basis of their JAK2 status (V617F-positive or V617F-negative), with a continuum between V617F-positive ET and polycythemia vera (PV). Nevertheless, increasingly contradictory data on the impact of JAK2-V617F (presence and load) on ET phenotype highlight the need for further investigations.

Materials And Methods: We investigated the influence of JAK2-V617F on ET phenotype using mass spectrometry-based analysis of serum protein profiles of ET patients, comparatively with PV patients.

Results: V617F-positive ET and PV displayed significant differences in their serum protein profiles. Furthermore, JAK2-V617F presence did not impact significantly the serum proteome of ET patients: we observed very few differences in serum protein profiles of V617F-positive and -negative ET. Reciprocally, clustering of ET patients on the basis of their serum protein profiles did not correlate with JAK2-V617F presence. Finally, the JAK2-V617F load did not influence serum apolipoprotein A-1 levels in ET, a previously validated marker of JAK2-V617F allele burden in PV.

Conclusion: Serum proteome of ET patients was not influenced by the presence of JAK2-V617F or by high V617F allelic ratio (up to 50%) suggesting that ET phenotype is, at best, only partially influenced by the JAK2-V617F mutation.