BACKGROUND: Myelofibrosis (MF) is the most aggressive Philadelphia-negative chronic myeloproliferative neoplasm (MPN) with high morbidity and mortality due to thrombo-hemorrhagic complications and leukemic transformation. MF is characterized by profound alterations of megakaryocytopoiesis, with consequent abnormalities in platelet number and function. We recently showed that the overexpression of the oncoprotein PKCepsilon plays a key role in the aberrant differentiation of MF megakaryocyte clone and that its levels correlate with disease burden. Moreover, our group previously demonstrated that PKCepsilon is over-expressed in platelets from patients with acute myocardial infarction (MI) and accounts for their increased reactivity. On these bases, we investigated here the activation state and PKCepsilon expression of MF platelets, testing potential correlations with thrombotic risk and disease aggressiveness. METHODS: Platelets were isolated from peripheral blood samples of MF patients and healthy donors (HDs). Patients were stratified according to the IPSS/DIPSS risk category and history of cardiovascular events. Platelet activation was assessed by flow cytometry. PKCepsilon mRNA and protein levels were determined by real time-PCR and western blot. RESULTS: MF platelets circulate in an activated status and display significantly higher levels of PKCepsilon compared to HDs. In MF patients, PKCepsilon platelet levels were associated with high-risk disease as well as with a positive history of major cardiovascular events. CONCLUSIONS: PKCepsilon is configuring as the common denominator of neoplastic transformation and thrombus formation in MF. Overall, our data pinpoint PKCepsilon as a potential novel biomarker of disease aggressiveness and thrombotic risk in this hematologic neoplasm.
BACKGROUND:Myelofibrosis (MF) is the most aggressive Philadelphia-negative chronic myeloproliferative neoplasm (MPN) with high morbidity and mortality due to thrombo-hemorrhagic complications and leukemic transformation. MF is characterized by profound alterations of megakaryocytopoiesis, with consequent abnormalities in platelet number and function. We recently showed that the overexpression of the oncoprotein PKCepsilon plays a key role in the aberrant differentiation of MF megakaryocyte clone and that its levels correlate with disease burden. Moreover, our group previously demonstrated that PKCepsilon is over-expressed in platelets from patients with acute myocardial infarction (MI) and accounts for their increased reactivity. On these bases, we investigated here the activation state and PKCepsilon expression of MF platelets, testing potential correlations with thrombotic risk and disease aggressiveness. METHODS: Platelets were isolated from peripheral blood samples of MF patients and healthy donors (HDs). Patients were stratified according to the IPSS/DIPSS risk category and history of cardiovascular events. Platelet activation was assessed by flow cytometry. PKCepsilon mRNA and protein levels were determined by real time-PCR and western blot. RESULTS: MF platelets circulate in an activated status and display significantly higher levels of PKCepsilon compared to HDs. In MF patients, PKCepsilon platelet levels were associated with high-risk disease as well as with a positive history of major cardiovascular events. CONCLUSIONS:PKCepsilon is configuring as the common denominator of neoplastic transformation and thrombus formation in MF. Overall, our data pinpoint PKCepsilon as a potential novel biomarker of disease aggressiveness and thrombotic risk in this hematologic neoplasm.
Authors: Giuseppe Lippi; Martina Montagnana; Gian Luca Salvagno; Nicola Cicorella; Maurizio Degan; Piero Minuz; Clara Lechi; Gian Cesare Guidi Journal: Int J Cardiol Date: 2006-07-03 Impact factor: 4.164
Authors: E Masselli; C Carubbi; G Gobbi; P Mirandola; D Galli; S Martini; S Bonomini; M Crugnola; L Craviotto; F Aversa; M Vitale Journal: Leukemia Date: 2015-06-19 Impact factor: 11.528
Authors: Amrei Strehl; Imke C A Munnix; Marijke J E Kuijpers; Paola E J van der Meijden; Judith M E M Cosemans; Marion A H Feijge; Bernhard Nieswandt; Johan W M Heemskerk Journal: J Biol Chem Date: 2007-01-08 Impact factor: 5.157
Authors: Francisco Cervantes; Brigitte Dupriez; Arturo Pereira; Francesco Passamonti; John T Reilly; Enrica Morra; Alessandro M Vannucchi; Ruben A Mesa; Jean-Loup Demory; Giovanni Barosi; Elisa Rumi; Ayalew Tefferi Journal: Blood Date: 2008-11-06 Impact factor: 22.113
Authors: Catherine J Pears; Kelly Thornber; Jocelyn M Auger; Craig E Hughes; Beata Grygielska; Majd B Protty; Andrew C Pearce; Steve P Watson Journal: PLoS One Date: 2008-11-24 Impact factor: 3.240
Authors: Elena Masselli; Cecilia Carubbi; Benedetta Cambò; Giulia Pozzi; Giuliana Gobbi; Prisco Mirandola; Elena Follini; Luca Pagliaro; Daniela Di Marcantonio; Francesco Bonatti; Antonio Percesepe; Stephen M Sykes; Franco Aversa; Marco Vitale Journal: Leukemia Date: 2018-03-06 Impact factor: 11.528