TY - JOUR
T1 - Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis
AU - Rumi, Elisa
AU - Pietra, Daniela
AU - Pascutto, Cristiana
AU - Guglielmelli, Paola
AU - Martínez-Trillos, Alejandra
AU - Casetti, Ilaria
AU - Colomer, Dolors
AU - Pieri, Lisa
AU - Pratcorona, Marta
AU - Rotunno, Giada
AU - Sant'Antonio, Emanuela
AU - Bellini, Marta
AU - Cavalloni, Chiara
AU - Mannarelli, Carmela
AU - Milanesi, Chiara
AU - Boveri, Emanuela
AU - Ferretti, Virginia
AU - Astori, Cesare
AU - Rosti, Vittorio
AU - Cervantes, Francisco
AU - Barosi, Giovanni
AU - Vannucchi, Alessandro M.
AU - Cazzola, Mario
PY - 2014/8/14
Y1 - 2014/8/14
N2 - 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 decisionmaking, but should also be considered in designing clinical trials.
AB - 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 decisionmaking, but should also be considered in designing clinical trials.
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U2 - 10.1182/blood-2014-05-578435
DO - 10.1182/blood-2014-05-578435
M3 - Article
C2 - 24986690
AN - SCOPUS:84905990634
VL - 124
SP - 1062
EP - 1069
JO - Blood
JF - Blood
SN - 0006-4971
IS - 7
ER -