Li Bing, Xu Junqing, Wang Jingya, Gale Robert Peter, Xu Zefeng, Cui Yajuan, Yang Lin, Xing Ruixian, Ai Xiaofei, Qin Tiejun, Zhang Yue, Zhang Peihong, Xiao Zhijian
MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, UK.
Haematologica. 2014 Nov;99(11):1697-700. doi: 10.3324/haematol.2014.109249. Epub 2014 Jul 4.
We tested 357 Chinese with primary myelofibrosis for mutations in CALR, JAK2 and MPL. CALR mutations were detected in 76 subjects (21%). There were 24 (32%) type-1 (L367fs46) and 49 (64%) type-2 (K385fs47) mutations. Seventy-two of 168 subjects (43%) without a JAK2 or MPL mutation had a CALR mutation. Subjects with a type-2 CALR mutation had lower hemoglobin concentrations (P=0.001), lower WBC counts (P<0.001), a higher percentage of blood blasts (P=0.009), and higher conventional (P<0.001) and Chinese-adjusted Dynamic International Prognostic Scoring System (P<0.001) scores compared with subjects with JAK2 mutations. Subjects with a type-2 CALR mutation were also likely to have abnormal platelet levels (<100 × 10(9)/L, P=0.01 or >450 × 10(9)/L, P=0.042) and no splenomegaly (P=0.004). Type-2 CALR mutation or no detectable mutation was an independent high-risk factor for survival in multivariate analyses. These data suggest the ratio between type-1 and type-2 mutations is reversed in Chinese with primary myelofibrosis compared with populations of subjects with primary myelofibrosis of predominately European descent. The unfavorable prognostic impact of CALR mutations in Chinese with primary myelofibrosis is only seen in those with type-2 mutations. These data underscore the need to evaluate the prognostic impact of genetic mutations in different populations.
我们检测了357例原发性骨髓纤维化的中国患者的CALR、JAK2和MPL基因突变情况。在76例受试者（21%）中检测到CALR基因突变。其中有24例（32%）1型（L367fs46）和49例（64%）2型（K385fs47）突变。168例无JAK2或MPL突变的受试者中有72例（43%）存在CALR突变。与JAK2基因突变的受试者相比，2型CALR基因突变的受试者血红蛋白浓度较低（P=0.001）、白细胞计数较低（P<0.001）、血原始细胞百分比更高（P=0.009），传统（P<0.001）和中国调整后的动态国际预后评分系统（P<0.001）评分更高。2型CALR基因突变的受试者也可能有血小板水平异常（<100×10⁹/L，P=0.01或>450×10⁹/L，P=0.042）且无脾肿大（P=0.004）。在多变量分析中，2型CALR基因突变或未检测到突变是生存的独立高危因素。这些数据表明，与主要为欧洲血统的原发性骨髓纤维化患者群体相比，中国原发性骨髓纤维化患者中1型和2型突变的比例相反。原发性骨髓纤维化中国患者中CALR基因突变的不良预后影响仅见于2型突变患者。这些数据强调了评估不同人群基因突变预后影响的必要性。
