CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: Clinical, cytogenetic and molecular comparisons

A. Tefferi, T. L. Lasho, C. M. Finke, R. A. Knudson, R. Ketterling, C. H. Hanson, M. Maffioli, D. Caramazza, F. Passamonti, A. Pardanani

Research output: Contribution to journalArticle

321 Scopus citations

Abstract

Calreticulin (CALR) mutations were recently described in JAK2 and MPL unmutated primary myelofibrosis (PMF) and essential thrombocythemia. In the current study, we compared the clinical, cytogenetic and molecular features of patients with PMF with or without CALR, JAK2 or MPL mutations. Among 254 study patients, 147 (58%) harbored JAK2, 63 (25%) CALR and 21 (8.3%) MPL mutations; 22 (8.7%) patients were negative for all three mutations, whereas one patient expressed both JAK2 and CALR mutations. Study patients were also screened for ASXL1 (31%), EZH2 (6%), IDH (4%), SRSF2 (12%), SF3B1 (7%) and U2AF1 (16%) mutations. In univariate analysis, CALR mutations were associated with younger age (P<0.0001), higher platelet count (P<0.0001) and lower DIPSS-plus score (P=0.02). CALR-mutated patients were also less likely to be anemic, require transfusions or display leukocytosis. Spliceosome mutations were infrequent (P=0.0001) in CALR-mutated patients, but no other molecular or cytogenetic associations were evident. In multivariable analysis, CALR mutations had a favorable impact on survival that was independent of both DIPSS-plus risk and ASXL1 mutation status (P=0.001; HR 3.4 for triple-negative and 2.2 for JAK2-mutated). Triple-negative patients also displayed inferior LFS (P=0.003). The current study identifies 'CALR-ASXL1 + ' and 'triple-negative' as high-risk molecular signatures in PMF.

Original languageEnglish (US)
Pages (from-to)1472-1477
Number of pages6
JournalLeukemia
Volume28
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • CALR
  • JAK2
  • myeloproliferative
  • prognosis
  • survival

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Tefferi, A., Lasho, T. L., Finke, C. M., Knudson, R. A., Ketterling, R., Hanson, C. H., Maffioli, M., Caramazza, D., Passamonti, F., & Pardanani, A. (2014). CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: Clinical, cytogenetic and molecular comparisons. Leukemia, 28(7), 1472-1477. https://doi.org/10.1038/leu.2014.3