Objective: To investigate the incidence, molecular features and clinical significance of RNA splicing machinery genes mutation in myelodysplastic syndromes (MDS) and related diseases. Methods: Mutational analysis of splicing factor 3B subunit 1 (SF3B1) (K700E) , U2 small nuclear RNA auxiliary factor 1 (U2AF1) (S34, Q157P) and serine/arginine-rich splicing factor 2 (SRSF2) (P95) in 118, de novo MDS and related diseases were separately performed by using polymerase chain reaction (PCR) followed by sequence analysis. Results: Of 118 MDS patients, 76 males and 42 females, the median age was 53.5 (13-84) years old. 19.49% (23/118) had SF3B1 (K700E) mutation. As compared with those with wild type SF3B1, patients with SF3B1 K700E were of older[58 (32-78) years vs 51 (13-84) years, z=-1.981, P=0.048], lower HGB level[63 (40-95) g/L vs 77 (34-144) g/L, z=-3.192, P=0.001], higher platelet counts[121 (22-888) ×10(9)/L vs 59 (6-1 561) ×10(9)/L, z=-3.305, P=0.001], lower bone marrow blast cell counts[0.007 (0-0.122) vs 0.017 (0-0.268) , z=-2.885, P=0.004], higher ring sideroblasts percent [0 (0-64%) vs 0 (0-58%) , z=-4.664, P<0.001]. Of 105 MDS patients, 21.9% had U2AF1 (S34, Q157P) mutations. Of 107 MDS patients, 8 patients (7.48%) had SRSF2 (P95) mutations. Patients with SRSF2 mutations were older at diagnosis, the median age was 63 (50-84) years old, including 4 cases RAEB-1. The ratio of mutation was 14.29% (4/28) , and three patients transformed to AML. SF3B1 K700E and SRSF2 P95H mutations coexisted in 1 patient, and SF3B1 K700E and U2AF1 S34Y mutations were found concomitantly in 2 patients. Conclusion: Only SF3B1 gene mutation was closely related to ring sideroblasts, it was the key to pathogenesis of MDS.
目的：探讨RNA剪接体复合物编码基因SF3B1、U2AF1和SRSF2突变在MDS及相关疾病中的突变率、突变特点及临床意义。方法：以118例MDS及相关疾病患者为研究对象，采用PCR扩增产物直接测序法分别检测SF3B1（K700E）、U2AF1（S34、Q157P）和SRSF2（P95）突变情况。结果： 118例MDS患者中，男76例，女42例，中位年龄53.5（13~84）岁。对全部患者均进行SF3B1（K700E）基因突变分析，SF3B1（K700E）的突变率为19.49%（118例中23例）。在突变的22例MDS患者中，14例环形铁粒幼红细胞（RS）比例≥15%，其中难治性贫血伴环状铁粒幼红细胞（RARS）7例、难治性血细胞减少伴有多系发育异常（RCMD）6例、难治性贫血（RA）1例。与未突变组相比，突变组患者的年龄偏大[58（32~78）岁对51（13~84）岁，z=-1.981，P=0.048]、PLT偏高[121（22~888）×10(9)/L对59（6~1 561）× 10(9)/L，z=-3.305，P=0.001]、骨髓原始细胞比例偏低[0.007（0~0.122）对0.017（0~0.268），z=-2.885，P=0.004]、RS比例偏高[0（0~64%）对0（0~58%），z=-4.664，P<0.001]，HGB偏低[63（40~95）g/L对77（34~144）g/L，z=-3.192，P=0.001]。对105例患者进行U2AF1（S34、Q157P）基因突变分析，突变率为21.90%（105例中23例）。突变组患者各临床特征与未突变组相比差异均无统计学意义。107例患者有SRSF2（P95）突变结果，8例突变，突变率为7.48%，突变组患者初诊时年龄偏高，中位年龄63（50~84）岁，其中难治性贫血伴有原始细胞增多-1（RAEB-1）4例，突变率为14.29%（28例中4例）；MDS转化的急性髓系白血病3例。1例患者同时出现SF3B1（K700E）和SRSF2（P95H）突变，2例患者同时出现SF3B1（K700E）和U2AF1（S34Y）突变。结论： SF3B1、U2AF1和SRSF2剪接体复合物蛋白编码基因中，仅SF3B1基因突变与环状铁粒幼红细胞增多性贫血密切相关，是该亚型的主要致病基因。.
Keywords: DNA mutational analysis; Gene, SF3B1; Gene, SRSF2; Gene, U2AF1; Myelodysplastic syndromes.