Frequency and allele burden of CALR mutations in Chinese with essential thrombocythemia and primary myelofibrosis without JAK2V617F or MPL mutations
Frequency and allele burden of CALR mutations in Chinese with essential thrombocythemia and primary myelofibrosis without JAK2V617F or MPL mutations
复制标题
无 JAK2V617F 或 MPL 突变的原发性血小板增多症和原发性骨髓纤维化患者中 CALR 突变的频率和等位基因负荷
DOI：
10.1016/j.leukres.2015.02.006
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发表时间：
2015-05-01
影响因子：
2.7
通讯作者：
Ruan, Guo-Rui
中科院分区：
文献类型：
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作者：
Li, Ning;Yao, Qiu-Mei;Ruan, Guo-Rui
在大约50%的具有JAK2和MPL野生型等位基因的欧洲血统的原发性血小板增多症（ET）或原发性骨髓纤维化（PMF）患者中检测到CALR突变。我们研究了1088名患有不同骨髓增殖性肿瘤的中国人，包括ET （N= 234）和PMF (N=50)，没有JAK2（V617F）或MPL外显子10突变。53%的ET患者（95% CI, 46-60%）和56%的PMF患者（95% CI, 41-70%）检测到CALR突变。共鉴定出152个CALR突变，分为15种类型，包括缺失型（N= 8）、插入型（N=3）和复杂型（N=4）。我们还发现了9个新的突变。平均（+/- SD）突变等位基因负荷为31 +/- 12%（范围0.5-69%）。PMF患者的CALR突变等位基因负担高于ET患者（38 +/- 8% vs. 29 +/- 12%; P < 0.001）。在CALR突变的人群中，PMF患者与ET患者具有不同的临床特征。这些数据可能对中国（约占所有ET和PMF患者的40%）的ET和PMF诊断和治疗反应监测有用。他们还强调了这些疾病的中国人和主要是欧洲血统的人在CALR突变上的异同。(C) 2015 Elsevier Ltd.版权所有。
CALR mutations are detected in about 50% of persons of predominately European descent with essential thrombocythemia (ET) or primary myelofibrosis (PMF) with wild-type alleles of JAK2 and MPL. We studied 1088 Chinese with diverse myeloproliferative neoplasms including ET (N= 234) and PMF (N=50) without JAK2(V617F) or MPL exon 10 mutations. CALR mutation was detected in 53% (95% CI, 46-60%) of subjects with ET and 56% (95% CI, 41-70%) of subjects with PMF. 152 CALR mutations were identified clustering into 15 types including deletions (N= 8), insertions (N=3) and complex indels (N=4). We also identified 9 new mutations. Mean (+/- SD) mutant allele burden was 31 +/- 12% (range, 0.5-69%). Persons with PMF had higher CALR mutant allele burdens than those with ET (38 +/- 8% vs. 29 +/- 12%; P < 0.001). Amongst persons with CALR mutations, those with PMF had different clinical features from those with ET. These data may be useful for diagnosing ET and PMF in Chinese who are about 40% of all persons with ET and PMF and for monitoring therapy-response. They also highlight similarities and differences in CALR mutations between Chinese and persons of predominately European descent with these diseases. (C) 2015 Elsevier Ltd. All rights reserved.