Abstract
Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 %), JAK2V617F in 94 (63.9 %), and MPL mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 %) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CARL mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 109/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.
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Acknowledgments
The study was supported by the National Science Council grant to CC Chen (NSC102-2314-B-182-047), Chang-Gung Memorial Hospital grants to CC Chen (CMRPG6B0221 and CMRPG6B0371), and Taipei Veterans General Hospital grant to JP Gau (VGH102C-202).
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All authors declare that there are no competing financial interests in relation to the work.
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Chih-Cheng Chen, Jyh-Pyng Gau, and Hui-Ju Chou contributed equally to this work.
Chih-Cheng Chen and Jyh-Pyng Gau share co-senior authorship.
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Chen, CC., Gau, JP., Chou, HJ. et al. Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia. Ann Hematol 93, 2029–2036 (2014). https://doi.org/10.1007/s00277-014-2151-8
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DOI: https://doi.org/10.1007/s00277-014-2151-8