Simultaneous screening for JAK2 and calreticulin gene mutations in myeloproliferative neoplasms with high resolution melting

Nariyoshi Matsumoto,Sayaka Mori,Hiroo Hasegawa,Daisuke Sasaki,Hayato Mori,Kazuto Tsuruda,Daisuke Imanishi,Yoshitaka Imaizumi,Tomoko Hata,Norihito Kaku,Kousuke Kosai,Naoki Uno,Yasushi Miyazaki,Katsunori Yanagihara

doi:10.1016/j.cca.2016.09.023

Nariyoshi Matsumoto, Sayaka Mori + Show 12 more

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https://doi.org/10.1016/j.cca.2016.09.023

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IntroductionRecently, novel calreticulin (CALR) mutations were discovered in Janus kinase 2 (JAK2) non-mutated myelofibrosis (PMF) and essential thrombocythemia (ET) cases, with a frequency of 60–80%. We examined clinical correlations and CALR mutation frequency in our myeloproliferative neoplasms (MPN) cases, and introduce an effective test method for use in clinical practice. MethodsWe examined 177 samples previously investigated for the JAK2 mutation for differential diagnosis of MPN. JAK2 and CALR mutations were analyzed using melting curve analysis and microchip electrophoresis, respectively. Next, we constructed a test for simultaneous screening of the JAK2 and CALR mutations utilizing high resolution melting (HRM). ResultsAmong 99 MPN cases, 60 possessed the JAK2 mutation alone. Of the 39 MPN cases without the JAK2 mutation, 14 were positive for the CALR mutation, all of which were ET. Using our novel screening test for the JAK2 and CALR mutations by HRM, the concordance rate of conventional analysis with HRM was 96% for the JAK2 mutation and 95% for the CALR mutation. ConclusionOur novel simultaneous screening test for the JAK2 and CALR gene mutations with HRM is useful for diagnosis of MPN.

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Recently, novel calreticulin (CALR) mutations were discovered in Janus kinase 2 (JAK2) non-mutated myelofibrosis (PMF) and essential thrombocythemia (ET) cases, with a frequency of 60–80%
Our novel simultaneous screening test for the JAK2 and CALR gene mutations with high resolution melting (HRM) is useful for diagnosis of myeloproliferative neoplasms (MPN)
We examined samples from 177 patients previously investigated for the presence of the JAK2 mutation for differential diagnosis of MPN in patients treated at Nagasaki University Hospital, between 2008 and

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Introduction

Novel calreticulin (CALR) mutations were discovered in Janus kinase 2 (JAK2) non-mutated myelofibrosis (PMF) and essential thrombocythemia (ET) cases, with a frequency of 60–80%. We examined clinical correlations and CALR mutation frequency in our myeloproliferative neoplasms (MPN) cases, and introduce an effective test method for use in clinical practice. Except for chronic myelogenous leukemia (CML), the 3 most common types of MPN are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In many cases, these diseases develop slowly and gradually worsen, while. Mutations in the thrombopoietin receptor gene (myeloproliferative leukemia, MPL) have been reported in patients with JAK2 mutation-negative MPN. Distinguishing ET cases possessing nonmutated JAK2 from the much more common reactive thrombocytosis remains a major diagnostic problem

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