CALR mutations in a cohort of JAK2 V617F negative patients with suspected myeloproliferative neoplasms

被引:14
作者
Mikic, Tanja Belcic [1 ,2 ]
Pajic, Tadej [1 ,3 ]
Sever, Matjaz [1 ,2 ]
机构
[1] Univ Med Ctr Ljubljana, Dept Haematol, Zaloska 7, Ljubljana 1000, Slovenia
[2] Univ Ljubljana, Fac Med, Korytkova 2, Ljubljana 1000, Slovenia
[3] Univ Maribor, Fac Med, Taborska Ulica 8, SLO-2000 Maribor, Slovenia
关键词
CALRETICULIN MUTATIONS; ESSENTIAL THROMBOCYTHEMIA; PRIMARY MYELOFIBROSIS; POLYCYTHEMIA-VERA; EXON-9; MUTATIONS; RISK-FACTORS; THROMBOSIS; MPL; SUBTYPES; CLASSIFICATION;
D O I
10.1038/s41598-019-56236-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Suspicion of myeloproliferative neoplasms (MPNs) and especially essential thrombocythemia (ET) in primary care is often based solely on blood counts, with patients referred to a haematologist without a thorough evaluation. We retrospectively assessed the role of calreticulin gene (CALR) mutations in the diagnosis of MPN in this population. We studied CALR mutations in 524 JAK2 V617F-negative patients with suspected MPN. Uncommon CALR mutations were confirmed by Sanger sequencing and searched for in the COSMIC or HGMD database. Mutations were defined as frameshift or non-frameshift mutations. CALR mutations were detected in 23 patients (23/524 = 4.4%). Four mutations detected in our study were newly identified mutations. Non-frameshift mutations were detected in two patients. Most patients (380/524 = 72.5%) were diagnosed with secondary conditions leading to blood count abnormalities such as iron deficiency, inflammatory and infectious diseases, malignancy and hyposplenism. Nine patients (9/23 = 39%) were retrospectively diagnosed with ET based on CALR mutation confirmation. Two patients with non-frameshift CALR mutations were diagnosed with reactive thrombocytosis and MPN unclassifiable, respectively. Our study showed that CALR mutations are important, non-invasive diagnostic indicators of ET and can aid in its diagnosis. Moreover, the type of CALR mutation must be accurately defined, as non-frameshift mutations may not be associated with ET. Finally, CALR mutation detection should be reserved for patients with high suspicion of clonal haematological disease.
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页数:9
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