title: JAK2 V617F, MPL, and CALR mutations in essential thrombocythaemia and major thrombotic complications: a single-institute retrospective analysis.
abstract: Thrombo-haemorrhagic events are the main cause of morbidity and mortality in essential thrombocythemia. The aim of this study was to estimate the incidence of thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R, W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential thrombocythaemia patients (72 females and 29 males with a mean age of 61 years) diagnosed in a Southern Hungarian regional academic centre. The incidence of major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F mutation. The MPL mutations were analysed by sequencing and the W515L was the only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET. Statistical analyses revealed that the JAK2V617F mutation was associated with significantly increased levels of platelet (p = 0.042), haemoglobin (p = 0.000), red blood cell (p = 0.000) and haematocrit (p = 0.000) and hepatomegaly (p = 0.045) at diagnosis compared to JAK2V617F negative counterparts, however there was no significant association between the JAK2V617F mutation status (relative risk: 1.297, 95 % CI 0.395-4.258; p = 0.668) and subsequent thrombotic complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the clinical findings at the diagnosis of ET was obvious, but their statistically significant role in the prediction of thrombotic events could not be proven in this study. Our results indirectly support the concept that, besides the quantitative and qualitative changes in the platelets, the mechanisms leading to thrombosis are more complex and multifactorial.
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Korányi fasor 6., H-6720, Szeged, Hungary, evaposfay@gmail.com.
authors.forename: Éva
authors.initials: É
authors.lastname: Pósfai
authors.forename: Imelda
authors.initials: I
authors.lastname: Marton
authors.forename: Péter Attila
authors.initials: PA
authors.lastname: Király
authors.forename: Balázs
authors.initials: B
authors.lastname: Kotosz
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kiss-László
authors.forename: Márta
authors.initials: M
authors.lastname: Széll
authors.forename: Zita
authors.initials: Z
authors.lastname: Borbényi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D037282:Calreticulin / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013920:Thrombocythemia, Essential / Q000150:complications / Q000235:genetics* / Q000401:mortality; D013927:Thrombosis / Q000150:complications / Q000235:genetics* / Q000401:mortality; D055815:Young Adult
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2