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.

Apolipoprotein A1: A new serum marker correlated to JAK2 V617F proportion at diagnosis in patients with polycythemia vera.

Polycythemia vera (PV) is a myeloproliferative disorder (MPD) characterized by an acquired gain-of-function mutation of the JAK2 protein (JAK2 V617F). Allele-specific quantitative PCR has showed a JAK2 V617F dosage effect on haematological and clinical parameters of PV at diagnosis, but it is unknown whether the level of certain serum proteins might correlate with the proportion of mutated JAK2. Taking into account that such proteins could represent useful prognostic marker, we investigated the serum protein profile of PV patients by SELDI-TOF MS. We identified apolipoprotein A1 (Apo-A1) as a serum marker correlated to the percentage of JAK2 V617F alleles; Apo-A1 expression being the highest for PV patients with more than 75% of mutated alleles. Immuno-assay on an automated random immuno-analyser confirmed the correlation between Apo-A1 concentrations and JAK2 V617F percentages, and showed that serum Apo-A1 assay allowed the specific discrimination of PV patients with high levels of mutated alleles (≥75%). These data suggest that Apo-A1 assay could be a useful assay for the stratification of PV patients at diagnosis.