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Driver Mutations and Prognosis in PMF Assessed

Am J Hematol; ePub 2017 November 22; Tefferi, et al

Type 1/like calreticulin mutations in people with primary myelofibrosis (PMF) predict superior survival and appear to partially alter the harmful effects of high molecular risk mutations, according to a study involving nearly 1,100 individuals. Investigators assessed the prognostic distinction between type 1/like and type 2/like calreticulin mutations, as well as the detrimental effect of triple-negative mutational status in participants from the Mayo Clinic (n=708), and verified the results in a second cohort (n=386). Among the results:

  • Two-thirds of patients harbored JAK2; 16% calreticulin type 1/like; 3% calreticulin type 2/like; 5% MPL mutations; 10% were triple-negative.
  • People with type 1/like calreticulin were ~twice as likely to experience longer survival when compared with each of the other mutations.
  • Absence of type 1/like calreticulin, presence of ASXL1/SRSF2 mutations, and DIPSS-plus each predicted inferior survival.
  • Patients with ASXL1/SRSF2 mutations with type 1/like calreticulin mutations survived an average of nearly 6 years, twice as long as those without such mutations.
  • Triple-negative status did not reveal prognostic information with regards to overall or leukemia-free survival.


Tefferi A, Nicolosi M, Mudireddy M. Driver mutations and prognosis in primary myelofibrosis: Mayo-Careggi MPN alliance study of 1,095 patients. [Published online ahead of print November 22, 2017]. Am J Hematol. 2017 Nov 22. doi:10.1002/ajh.24978.