Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study
Background: Recently, calreticulin (CALR) gene mutations have been identified in patients with essential thrombocythemia (ET). A high-frequency of ET cases without Janus kinase 2 (JAK2) mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2016-01-01
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| Series: | Chinese Medical Journal |
| Subjects: | |
| Online Access: | http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=15;spage=1778;epage=1783;aulast=Sun |
| _version_ | 1818843191894343680 |
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| author | Chao Sun Xin Zhou Zhi-Jian Zou Hong-Feng Guo Jian-Yong Li Chun Qiao |
| author_facet | Chao Sun Xin Zhou Zhi-Jian Zou Hong-Feng Guo Jian-Yong Li Chun Qiao |
| author_sort | Chao Sun |
| collection | DOAJ |
| description | Background: Recently, calreticulin (CALR) gene mutations have been identified in patients with essential thrombocythemia (ET). A high-frequency of ET cases without Janus kinase 2 (JAK2) mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET.
Methods: We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2V617F, and MPLW515 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features.
Results: CALR, JAK2V617F, and MPLW515 mutations were detected in 30% (n = 92), 48% (n = 149), and 1% (n = 4) of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 (52-bp deletion) and Type 2 (5-bp insertion, TTGTC) mutations, leading to del367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell (WBC) count, and higher platelet count compared to those with mutated JAK2 (P < 0.05). Furthermore, a significant difference was found in WBCs between wild-type patients (triple negative for JAK2, MPL, and CALR mutations) and patients with JAK2 mutations. Patients with CALR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET (P < 0.05).
Conclusions: CALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared with JAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, CALR is a potentially valuable diagnostic marker and therapeutic target in ET. |
| first_indexed | 2024-12-19T04:53:57Z |
| format | Article |
| id | doaj.art-8422c2092ed74f7b9e62a10564167fac |
| institution | Directory Open Access Journal |
| issn | 0366-6999 |
| language | English |
| last_indexed | 2024-12-19T04:53:57Z |
| publishDate | 2016-01-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj.art-8422c2092ed74f7b9e62a10564167fac2022-12-21T20:35:16ZengWolters KluwerChinese Medical Journal0366-69992016-01-01129151778178310.4103/0366-6999.186641Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical StudyChao SunXin ZhouZhi-Jian ZouHong-Feng GuoJian-Yong LiChun QiaoBackground: Recently, calreticulin (CALR) gene mutations have been identified in patients with essential thrombocythemia (ET). A high-frequency of ET cases without Janus kinase 2 (JAK2) mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET. Methods: We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2V617F, and MPLW515 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features. Results: CALR, JAK2V617F, and MPLW515 mutations were detected in 30% (n = 92), 48% (n = 149), and 1% (n = 4) of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 (52-bp deletion) and Type 2 (5-bp insertion, TTGTC) mutations, leading to del367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell (WBC) count, and higher platelet count compared to those with mutated JAK2 (P < 0.05). Furthermore, a significant difference was found in WBCs between wild-type patients (triple negative for JAK2, MPL, and CALR mutations) and patients with JAK2 mutations. Patients with CALR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET (P < 0.05). Conclusions: CALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared with JAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, CALR is a potentially valuable diagnostic marker and therapeutic target in ET.http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=15;spage=1778;epage=1783;aulast=SunCalreticulin; Essential Thrombocythemia; Gene Mutation; Janus Kinase 2 |
| spellingShingle | Chao Sun Xin Zhou Zhi-Jian Zou Hong-Feng Guo Jian-Yong Li Chun Qiao Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study Chinese Medical Journal Calreticulin; Essential Thrombocythemia; Gene Mutation; Janus Kinase 2 |
| title | Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study |
| title_full | Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study |
| title_fullStr | Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study |
| title_full_unstemmed | Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study |
| title_short | Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study |
| title_sort | clinical manifestation of calreticulin gene mutations in essential thrombocythemia without janus kinase 2 and mpl mutations a chinese cohort clinical study |
| topic | Calreticulin; Essential Thrombocythemia; Gene Mutation; Janus Kinase 2 |
| url | http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=15;spage=1778;epage=1783;aulast=Sun |
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