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.


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.


CONCLUSIONS
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.
Laboratoire d'hématologie cellulaire et moléculaire, DBPC, CHU Grenoble, France. PMossuz@chu-grenoble.fr
Pascal
P
Mossuz
Marie
M
Arlotto
Sylvie
S
Hermouet
Ali
A
Bouamrani
Eric
E
Lippert
François
F
Girodon
Irène
I
Dobo
Praloran
P
Vincent
Jean Yves
JY
Cahn
François
F
Berger
D019943:Amino Acid Substitution; D001798:Blood Proteins / Q000032:analysis*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000097:blood* / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D011087:Polycythemia Vera / Q000097:blood / Q000235:genetics; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000235:genetics
D001798:Blood Proteins; D020543:Proteome; C507924:JAK2 protein, human; D053614:Janus Kinase 2