慢性中性粒细胞白血病CSF3R、ASXL1、SETBP1、JAK2 V617F和CALR基因突变研究

CSF3R, ASXL1, SETBP1, JAK2 V617F and CALR mutations in chronic neutrophilic leukemia

目的 探讨中性粒细胞白血病（CNL）患者CSF3R、ASXL1、SETBP1、JAK2 V617F和CALR基因突变情况.方法 依据2008年WHO造血组织和淋巴组织肿瘤分类标准对12例临床疑诊“CNL”患者进行回顾性诊断.采用直接测序法检测CSF3R、ASXL1、SETBP1和CALR基因突变,采用等位基因特异性聚合酶链反应（AS-PCR）检测JAK2 V617F突变.结果 6例确诊为CNL,2例诊断为意义未明的单克隆免疫球蛋白病（MGUS）伴CNL表现,4例诊断为感染、炎症或肿瘤继发的反应性中性粒细胞增多.6例CNL患者均伴有CSF3R T618I突变,其中1例为CSF3R单独突变,4例合并ASXL1及SETBP1突变,1例合并CALR突变（c.1154-1155insTTGTC）.2例MGUS伴CNL表现及4例反应性中性粒细胞增多患者均不伴有CSF3R、ASXL1、SETBP1或CALR基因突变.所有患者均无JAK2 V617F突变.结论 CSF3R、ASXL1和SETBP1基因突变是CNL患者常见的基因突变,以CSF3R T618I最为常见.将CSF3R、ASXL1和SETBP1基因突变的检测纳入CNL诊断标准可以提高诊断的准确性.

Objective To observe the CSF3R,ASXL1,SETBP1,JAK2 V617F and CALR mutations in patients with chronic neutrophilic leukemia （CNL）.Methods Twelve suspected CNL patients were retrospectively reviewed according the WHO criteria （2008）.CSF3R,ASXL1,SETBP1 and CALR mutations were sequenced,and JAK2 V617F was tested by allele specific （AS）-PCR.Results 6 of 12 cases were diagnosed as CML,and all of the 6 carried.4 of 6 patients also had ASXL1 and SETBP1 mutations and one had a CALR mutation （c.1154-1155insTTGTC）.Two patients with monoclonal gammopathy with uncertain significance （MGUS） combined with CNL-like symptoms had no CSF3R,ASXL1,SETBP1,JAK2 V617F or CALR mutation.The same results were also seen in other 4 cases with secondary neutrophilic leukocytosis.Conclusion CSF3R,ASXL1 and SETBP1 mutations differential diagnosis of CNL,and should be included in the diagnostic protocol so as to improve diagnostic accuracy for CNL.