Objective: The World Health Organization (WHO) embedded calreticulin receptor (CalR) and myeloproliferative leukemia virus (MPL) gene mutation in diagnostic criteria for primary myelofibrosis (PMF) and essential thrombocythemia (ET), since 2016). We aimed to identify the frequency of CalR and MPL gene mutations and their effects on clinical outcomes in bcr-Abl and Jak2 unmutated chronic myeloproliferative neoplasms (MPNs).
Methodology: We screened bcr-abl negative and Jak2 unmutated MPNs diagnosed and treated between March 2004 and January 2013 at İstanbul Medical Faculty. We revised the MPN diagnosis according to the latest WHO classification. The association of CalR and MPL mutation with thrombotic complications, leukemic transformation, and survival was was defined.
Results: A total of 46 ET (n=34) and PMF (n=12) patients enrolled in the study. The demographic characteristics were similar between the two disease groups. Patients’ mean age was 53.5 years (range 23–93 years) and gender distribution as 18 male to 28 female. A total of 18 patients (39.1%) had CalR mutation, and 4 (8.69%) patients MPL mutation. None of the ET patients had MPL mutations. CalR positive PMF patients’ mean age was lower compared to patients without the mutation (p: 0.028). During the follow-up period, 8.3% of PMF and 5.9% of ET patients experienced leukemic transformation. None of the leukemic transformed patients had gene mutations. Among thrombosis complications, six patients developed thrombosis. All of them were ET patients, and 3 of them had CalR mutation two as CalR type 1 and one as CalR type 2. The mortality ratio was higher in patients in PMF, regardless of mutational status (p: 0.006).
Conclusion: Our study cohort is small to make a definite conclusion. Apart from the diagnostic guide, CALR mutations seem to have a prognostic effect is different in PMF and ET. This prognostic significance of CALR could be different among the MPN categories.