中文摘要：

目的探讨JAK2V617F与慢性骨髓增殖性疾病（cMPD）的关系。方法对523例cMPD患者按WHO标准进行回顾性诊断。应用等位基因特异性聚合酶链反应（ASP—PCR）检测JAK2V617F突变情况，用PCR-限制性片段长度多态性（RFLP）检测JAK2V617F（＋）者突变状态，根据PCR联合测序分析结果按突变位点T／G比值分析JAK2V617F突变负荷。比较JAK2V617F不同负荷与患者临床及实验室特征的关系。对JAK2V617F（-）者，通过PCR联合测序检测MPLW515L突变。结果523例cMPD患者共检出JAK2V617F（＋）者346例（66％），其中116例真性红细胞增多症（PV）患者检出109例（94％），153例原发性血小板增多症（ET）患者检出122例（80％），142例原发性骨髓纤维化（PMF）患者检出111例（78％），4例cMPD不能分类（cMPD—U）患者检出3例（75％），7例高嗜酸粒细胞增多症（HES）患者检出1例（14％），慢性粒细胞白血病（CML）和慢性嗜酸粒细胞白血病（CEL）未发现存在突变。346例JAK2V617F（＋）患者中5例为纯合子突变（PV4例，ET1例）。JAK2V617F突变以低负荷为主（71．5％），突变负荷以PV组最大，ET其次，PMF负荷最小（P=0．003）。PV患者血红蛋白水平与V617F突变负荷呈明显正相关（r=0．203，P=0．033）。ET患者骨髓巨核细胞数与JAK2V617F突变负荷呈正相关（r=0．205，P=0．024）；PMF高突变负荷组患者肝肿大发生率以及肝肿大程度均明显高于低负荷组（P值分别为0．003，0．001），并且肝肿大程度与突变负荷呈明显正相关（r=0．315，P=0．001）。JAK2V617F突变及其突变负荷与cMPD患者年龄、性别、血栓形成、高血压、脾肿大、白细胞计数、血小板计数、骨髓增生程度、骨髓纤维化及骨髓原始细胞比例均无明显相关性。结论①cMPD患者存在JAK2V617F突变，突变检出率从高到低分别为PV、ET、MF、cMPD—U、HES，CML、CEL中未发现此突变；@J

英文摘要：

Objective To investigate JAK2V617F mutation and its clinical significance in patients with chronic myeloproliferative disorders （cMPD）. Methods A retrospective study was performed on 523 cMPD patients diagnosed according to the current World Health Organization （WHO） criteria. Allele-specific PCR （ASP） was used to identify JAK2V617F mutation, the mutation status was analyzed by PCR-RFLP, and the results were confirmed by sequence analysis. The mutation burden was calculated by the ratio of T/G. The correlation between the allele burden and the clinical and hematologic features was analysed. For those without JAK2 V617F, MPL WS15L mutation was analyzed. Results JAK2 V617F was detected in 66% of all patients （94% in PV, 80% in ET, 78% in CIMF, 75% in CMPD-U and 14% in HES）. The majority of patients carried JAK2 V617F mutation were heterozygous , homozygote was found in only 5 cases （4 in PV and 1 in ET）. The mutation burden in most patients （71.5%） was low with PV 〉 ET 〉 CIMF （P = 0. 003 ）. Hemoglobin level was significantly related to high mutation burden in PV （r = 0. 203, P = 0.033 ）. Bone marrow megakaryocyte counts were found to be marked increased in ET with high JAK2 V617F loads （P = 0.024）,and hepatomegaly in CIMF was significantly associated with high JAK2 V617 F mntion burden （r = 0. 315, P = 0. 001 ）. Conclusions （1）Most cMPD patients, espeeialy those with PV, carry JAK2 V617F mutation, except for CML. （2）. 98% of JAK2 V617F mutation occurs of heterozygous status. （3）The mutation burden is PV 〉 ET 〉 CIMF. High JAK2 V617F loads are significantly associated with higher hemoglobin level in PV and higher bone marrow megakaryocyte counts in ET. （4）The positive correlation between hepatomegaly and JAK2 V617F mutation burden is found in CIMF.