Li M Y, Chao H Y, Sun A N, Qiu H Y, Jin Z M, Tang X W, Han Y, Fu C C, Chen S N, Wu D P
Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Jiangsu Clinical Medicine Center, Suzhou 215006, China.
Zhonghua Xue Ye Xue Za Zhi. 2017 Apr 14;38(4):295-300. doi: 10.3760/cma.j.issn.0253-2727.2017.04.007.
To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group. The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing. ① The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. ②The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] (<0.001) , but not for patients with CALR[57 (17-89) y] or MPL mutation[59 (22-71) y] (>0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level (<0.05) when compared with patients with CALR mutation or without mutations, or only significantly higher white blood cell count when compared with patients with MPL mutation (=0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×10(9)/L 800 (198-3 730) ×10(9)/L, <0.001]. ③Karyotype analysis was conducted in 1 160 patients with MPNs, the rates of karyotype abnormality of patients with and without CALR mutation were 9.8% (8/82) and 7.4% (80/1 078) (=0.441) respectively; The rates of karyotype abnormality of patients with and without JAK2V617F mutation were 7.7% (75/971) and 6.9% (13/189) (=0.688) respectively. The incidence of karyotype abnormality of patients with CALR mutation was higher than of with JAK2V617F[9.8% (8/82) 7.7% (75/971) ] without statistically significant difference (=0.512) . The karyotype analysis of 7 cases of JAK2 exon12 mutation and 6 ones with MPL gene mutation revealed normal karyotype. Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter lead to unique clinical phenotype.
探讨费城染色体阴性骨髓增殖性肿瘤（MPNs）患者中JAK2、CALR和MPL基因突变的发生率及突变类型，并比较不同突变类型与突变阴性组的临床特征。采用直接测序法检测1648例Ph阴性MPNs患者的JAK2 V617F、JAK2基因第12外显子、CALR基因第9外显子和MPL基因第10外显子的突变情况。①在508例真性红细胞增多症（PV）患者中，471例（92.7%）检测到JAK2V617F突变；在1049例原发性血小板增多症（ET）患者中，819例（78.1%）检测到该突变；在91例原发性骨髓纤维化（PMF）患者中，74例（81.3%）检测到该突变，总突变率为82.8%（1364/1648）。在508例PV患者中，9例（1.7%）检测到JAK2第12外显子突变，ET和PMF患者中未检测到该突变，总突变率为0.5%（9/1648）。在1049例ET患者中，132例（12.6%）检测到CALR突变；在91例PMF患者中，11例（12.1%）检测到该突变，总突变率为8.7%（143/1648）；在1049例ET患者中，9例（0.9%）检测到MPL突变；在91例PMF患者中，1例（1.1%）检测到该突变，总突变率为0.6%（10/1648）。直接测序未检测到任何两种驱动基因突变的共现情况。②JAK2V617F突变患者的中位发病年龄[61（15 - 95）岁]显著高于JAK2第12外显子突变患者[49（33 - 62）岁]或无突变患者[42（3 - 78）岁]（<0.001），但CALR突变患者[57（17 - 89）岁]或MPL突变患者[59（22 - 71）岁]与前两者相比差异无统计学意义（>0.05）。与CALR突变患者或无突变患者相比，JAK2V617F突变患者的白细胞计数和血红蛋白水平更高（<0.05），与MPL突变患者相比，仅白细胞计数显著更高（=0.013）。CALR突变患者的血小板计数显著高于JAK2V617F突变患者[966（400 - 2069）×10⁹/L对800（198 - 3730）×10⁹/L，<0.001]。③对1160例MPNs患者进行核型分析，CALR突变患者和无CALR突变患者的核型异常率分别为9.8%（8/82）和7.4%（80/1078）（=0.441）；JAK2V617F突变患者和无JAK2V617F突变患者的核型异常率分别为7.7%（75/971）和6.9%（13/189）（=0.688）。CALR突变患者的核型异常发生率高于JAK2V617F突变患者[9.8%（8/82）对7.7%（75/971）]，但差异无统计学意义（=0.512）。对7例JAK2第12外显子突变患者和6例MPL基因突变患者进行核型分析，结果显示核型正常。驱动基因突变检测可使MPNs的诊断和预后判断更可靠，MPNs的不同亚型具有不同的驱动基因突变谱，后者导致独特的临床表型。
