Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis
Elisa Rumi, Daniela Pietra, Cristiana Pascutto, Paola Guglielmelli, Alejandra Martínez-Trillos, Ilaria Casetti, Dolors Colomer, Lisa Pieri, Marta Pratcorona, Giada Rotunno, Emanuela Sant'Antonio, Marta Bellini, Chiara Cavalloni, Carmela Mannarelli, Chiara Milanesi, Emanuela Boveri, Virginia Ferretti, Cesare Astori, Vittorio Rosti, Francisco Cervantes, Giovanni Barosi, Alessandro M Vannucchi, Mario Cazzola, Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators, Alessandro M Vannucchi, Manjola Balliu, Niccolò Bartalucci, Flavia Biamonte, Andrea Bisognin, Costanza Bogani, Stefania Bortoluzzi, Alberto Bosi, Alessandro Coppe, Tiziana Fanelli, Rajmonda Fjerza, Paola Guglielmelli, Idalba Loiacono, Carmela Mannarelli, Roberto Marchioli, Serena Martinelli, Arianna Masciulli, Alessandro Pancrazzi, Chiara Paoli, Lisa Pieri, Giada Rotunno, Claudia Saccoman, Ambra Spolverini, Maria Chiara Susini, Lorenzo Tozzi, Giovanni Barosi, Cristina Azzan, Stefania Badalucco, Alessandra Balduini, Elisa Bonetti, Rita Campanelli, Paolo Catarsi, Antonina Maria Isgrò, Maria Letizia Lupo, Umberto Magrini, Margherita Massa, Valentina Poletto, Vittorio Rosti, Laura Villani, Mario Cazzola, Ilaria Ambaglio, Paolo Bernasconi, Ilaria Carola Casetti, Silvia Catricalà, Chiara Elena, Elena Fugazza, Anna Gall, Luca Malcovati, Chiara Milanesi, Cristiana Pascutto, Daniela Pietra, Francesco Ripamonti, Marianna Rossi, Elisa Rumi, Elisabetta Dejana, Ferruccio Breviario, Monica Corada, Benedetta Gaia Erba, Alessandro Rambaldi, Ariel Amaru, Tiziano Barbui, Clara Belotti, Chiara Boroni, Maria Luisa Ferrari, Guido Finazzi, Maria Chiara Finazzi, Josée Golay, Giuseppe Gritti, Silvia Salmoiraghi, Daniela Cilloni, Valentina Campia, Sonia Carturan, Angelo Guerrasio, Rossella Manfredini, Elisa Bianchi, Simona Salati, Enrico Tagliafico, Elena Tenedini, Roberta Zini, Elisa Rumi, Daniela Pietra, Cristiana Pascutto, Paola Guglielmelli, Alejandra Martínez-Trillos, Ilaria Casetti, Dolors Colomer, Lisa Pieri, Marta Pratcorona, Giada Rotunno, Emanuela Sant'Antonio, Marta Bellini, Chiara Cavalloni, Carmela Mannarelli, Chiara Milanesi, Emanuela Boveri, Virginia Ferretti, Cesare Astori, Vittorio Rosti, Francisco Cervantes, Giovanni Barosi, Alessandro M Vannucchi, Mario Cazzola, Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators, Alessandro M Vannucchi, Manjola Balliu, Niccolò Bartalucci, Flavia Biamonte, Andrea Bisognin, Costanza Bogani, Stefania Bortoluzzi, Alberto Bosi, Alessandro Coppe, Tiziana Fanelli, Rajmonda Fjerza, Paola Guglielmelli, Idalba Loiacono, Carmela Mannarelli, Roberto Marchioli, Serena Martinelli, Arianna Masciulli, Alessandro Pancrazzi, Chiara Paoli, Lisa Pieri, Giada Rotunno, Claudia Saccoman, Ambra Spolverini, Maria Chiara Susini, Lorenzo Tozzi, Giovanni Barosi, Cristina Azzan, Stefania Badalucco, Alessandra Balduini, Elisa Bonetti, Rita Campanelli, Paolo Catarsi, Antonina Maria Isgrò, Maria Letizia Lupo, Umberto Magrini, Margherita Massa, Valentina Poletto, Vittorio Rosti, Laura Villani, Mario Cazzola, Ilaria Ambaglio, Paolo Bernasconi, Ilaria Carola Casetti, Silvia Catricalà, Chiara Elena, Elena Fugazza, Anna Gall, Luca Malcovati, Chiara Milanesi, Cristiana Pascutto, Daniela Pietra, Francesco Ripamonti, Marianna Rossi, Elisa Rumi, Elisabetta Dejana, Ferruccio Breviario, Monica Corada, Benedetta Gaia Erba, Alessandro Rambaldi, Ariel Amaru, Tiziano Barbui, Clara Belotti, Chiara Boroni, Maria Luisa Ferrari, Guido Finazzi, Maria Chiara Finazzi, Josée Golay, Giuseppe Gritti, Silvia Salmoiraghi, Daniela Cilloni, Valentina Campia, Sonia Carturan, Angelo Guerrasio, Rossella Manfredini, Elisa Bianchi, Simona Salati, Enrico Tagliafico, Elena Tenedini, Roberta Zini
Abstract
We studied the impact of driver mutations of JAK2, CALR, (calreticulin gene) or MPL on clinical course, leukemic transformation, and survival of patients with primary myelofibrosis (PMF). Of the 617 subjects studied, 399 (64.7%) carried JAK2 (V617F), 140 (22.7%) had a CALR exon 9 indel, 25 (4.0%) carried an MPL (W515) mutation, and 53 (8.6%) had nonmutated JAK2, CALR, and MPL (so-called triple-negative PMF). Patients with CALR mutation had a lower risk of developing anemia, thrombocytopenia, and marked leukocytosis compared with other subtypes. They also had a lower risk of thrombosis compared with patients carrying JAK2 (V617F). At the opposite, triple-negative patients had higher incidence of leukemic transformation compared with either CALR-mutant or JAK2-mutant patients. Median overall survival was 17.7 years in CALR-mutant, 9.2 years in JAK2-mutant, 9.1 years in MPL-mutant, and 3.2 years in triple-negative patients. In multivariate analysis corrected for age, CALR-mutant patients had better overall survival than either JAK2-mutant or triple-negative patients. The impact of genetic lesions on survival was independent of current prognostic scoring systems. These observations indicate that driver mutations define distinct disease entities within PMF. Accounting for them is not only relevant to clinical decision-making, but should also be considered in designing clinical trials.
© 2014 by The American Society of Hematology.
Figures
Source: PubMed