The frequency of JAK2 exon 12 mutations in idiopathic erythrocytosis patients with low serum erythropoietin levels
The frequency of JAK2 exon 12 mutations in idiopathic erythrocytosis patients with low serum erythropoietin levels
复制标题
血清促红细胞生成素水平低的特发性红细胞增多症患者JAK2外显子12突变频率
DOI：
10.3324/haematol.11643
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发表时间：
2007
期刊：
影响因子：
10.1
通讯作者：
M. McMullin
中科院分区：
文献类型：
--
作者：
M. Percy;L. Scott;W. Erber;C. Harrison;J. Reilly;F. Jones;A. Green;M. McMullin
背景与目的特发性红细胞增多症(Idiopathic Ethercell sis，IE)以无巨核细胞或粒细胞增生的红细胞增多症为特征，与血清促红细胞生成素(EPO)水平变化有关。大多数IE患者缺乏JAK2 V617F突变，而大多数真性红细胞增多症患者都会发生这种突变。最近有四个新的JAK2突变等位基因在V617F阴性的伴有红细胞增多的骨髓增殖性疾病患者中被描述。本研究的目的是评估JAK2外显子12突变在IE患者中的患病率，并确定相关的临床病理特征。设计与方法从181例确诊为IE的患者中筛选出58例血清EPO水平低至正常，且无已知致病突变的IE患者。通过等位基因特异性聚合酶链式反应和测序对患者的DNA样本进行JAK2外显子12突变的筛查。用免疫组织化学方法检测骨髓环磷脂的形态异常和红系活性。结果共检出8例突变阳性病例，其中1例为JAK2基因突变外显子12，1例为双等位基因。突变阳性和突变阴性患者的血液学特征相似，尽管EPO超敏红系祖细胞仅发生在外显子12突变的患者中(p=0.0002；n=15)。由于红系增生，患者的骨髓呈中度高细胞状态，少数患者有轻度巨核细胞异型性。解释和结论在27%的血清EPO水平较低的患者中检测到JAK2外显子12突变，这些患者都有EPO非依赖的红系祖细胞。因此，出现这些特征之一的IE患者应该接受JAK2突变的检测。
Background and Objectives Idiopathic erythrocytosis (IE) is characterized by erythrocytosis in the absence of megakaryocytic or granulocytic hyperplasia, and is associated with variable serum erythropoietin (Epo) levels. Most patients with IE lack the JAK2 V617F mutation that occurs in the majority of polycythemia vera patients. Four novel JAK2 mutant alleles have recently been described in patients with V617F-negative myeloproliferative disorders presenting with erythrocytosis. The aims of this study were to assess the prevalence of JAK2 exon 12 mutations in IE patients, and to determine the associated clinicopathological features. Design and Methods A cohort of 58 IE patients with low to normal serum Epo levels and no known causative mutation were identified from 181 individuals diagnosed with IE. Patients’ DNA samples were screened for the presence of a JAK2 exon 12 mutation by allele-specific polymerase chain reaction and sequencing. Bone marrow trephines were examined for morphological abnormalities and the erythroid activity assessed immunohistochemically. Results Eight mutation-positive cases were identified, including one with a previously undescribed mutant JAK2 exon 12 allele and another with biallelic involvement. The hematologic features of mutation-positive and mutation-negative patients were similar, although Epo-hypersensitive erythroid progenitors occurred exclusively in patients with an exon 12 mutation (p=0.0002; n=15). Patients’ bone marrows were moderately hypercellular, as the result of erythroid hyperplasia, and several had mild megakaryocyte atypia. Interpretation and Conclusions JAK2 exon 12 mutations were detected in 27% of patients with low serum Epo levels, all of whom had Epo-independent erythroid progenitors. Consequently, IE patients presenting with either of these features should be tested for the presence of a JAK2 mutation.