Genetic Characteristics of Polycythemia Vera and Essential Thrombocythemia in Korean Patients

被引：1

作者：

Yoo, Eun-Hyung ^{[1
]}

Park, Kyung-Jin ^{[2
,3
]}

Won, Hong-Hee ^{[2
,3
]}

Park, Jun-Hee ^{[2
,3
]}

Park, Jong-Ho ^{[2
,3
]}

Lee, Seung-Tae ^{[4
]}

Kim, Hee-Jin ^{[4
]}

Bang, Soo-Mee ^{[5
]}

Chi, Hyun-Sook ^{[6
,7
]}

Jung, Chul Won ^{[8
]}

Kim, Sun-Hee ^{[4
]}

Yun, Hongseok ^{[9
]}

Sun, Choong-Hyun ^{[9
]}

Park, Inho ^{[9
]}

Lee, Seungmook ^{[9
]}

Lee, Clarence ^{[10
]}

Merriman, Barry ^{[10
]}

Luo, Raymond ^{[11
]}

Tan, Eileen Hwee Hong ^{[11
]}

Park, Keun-Joon ^{[12
]}

Yoo, Na-Kyung ^{[12
]}

Kang, Jason J. ^{[10
]}

Kim, Jong-Won ^{[4
]}

机构：

[1] Konyang Univ, Coll Med, Myunggok Med Res Inst, Dept Lab Med,Konyang Univ Hosp, Daejeon, South Korea

[2] Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, Seoul, South Korea

[3] Samsung Med Ctr, Samsung Biomed Res Inst, Seoul, South Korea

[4] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Lab Med & Genet, 81 Irwon Ro, Seoul 06351, South Korea

[5] Seoul Natl Univ, Coll Med, Bundang Hosp, Dept Internal Med, Songnam, South Korea

[6] Univ Ulsan, Dept Lab Med, Coll Med, Seoul, South Korea

[7] Asan Med Ctr, Seoul, South Korea

[8] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul, South Korea

[9] Samsung SDS, Seoul, South Korea

[10] Thermo Fisher Sci, Carlsbad, CA USA

[11] Thermo Fisher Sci, Singapore, Singapore

[12] Thermo Fisher Sci, Seoul, South Korea

来源：

JOURNAL OF CLINICAL LABORATORY ANALYSIS | 2016年 / 30卷 / 06期

关键词：

calreticulin; essential thrombocythemia; haplotype; polycythemia vera; whole-genome sequencing; JAK2; 46/1; HAPLOTYPE; MYELOPROLIFERATIVE NEOPLASMS; SOMATIC MUTATIONS; CALRETICULIN MUTATIONS; CONFERS SUSCEPTIBILITY; MYELOID DISORDERS; CHINESE PATIENTS; CALR MUTATIONS; RISK-FACTOR; PHENOTYPE;

D O I：

10.1002/jcla.21981

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

BackgroundDespite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET). MethodsWe conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. ResultsSeveral germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014). ConclusionThis study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.

引用

页码：1061 / 1070

页数：10

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