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 CervantesGiovanni Barosi, Alessandro M. Vannucchi, Mario Cazzola

Research output: Contribution to journalArticlepeer-review

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 decisionmaking, but should also be considered in designing clinical trials.

Original languageEnglish
Pages (from-to)1062-1069
Number of pages8
JournalBlood
Volume124
Issue number7
DOIs
Publication statusPublished - Aug 14 2014

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

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