骨髓增生异常综合征中医证型与遗传学及预后的相关性研究

Study on Correlation Among Traditional Chinese Medicine Syndrome Types,Genetics and Prognosis in Myelodysplastic Syndromes

目的:探讨骨髓增生异常综合征(MDS)患者中医证型与分子生物学、细胞遗传学及预后的相关性。方法:采用非参数秩和检验或卡方检验的统计学方法,回顾性分析85例初诊MDS患者的中医证型、外周血指标、疾病分型、分子生物学情况、细胞遗传学情况、预后情况,并探讨中医证型与其后几项之间的相关性。结果:85例MDS患者的中医证型以气阴两虚、毒瘀阻滞证为主,其次为脾肾两虚、毒瘀阻滞证和邪热炽盛、毒瘀阻滞证。邪热炽盛、毒瘀阻滞证患者的中性粒细胞绝对值(ANC)水平显著低于脾肾两虚、毒瘀阻滞证患者(P<0.01),气阴两虚、毒瘀阻滞证患者的血红蛋白(HGB)水平显著低于脾肾两虚、毒瘀阻滞证患者(P<0.001)。3组证型间疾病分型分布比较,差异有统计学意义(P<0.05);邪热炽盛、毒瘀阻滞证患者的疾病分型全为原始细胞增多型(EB型)。3组证型间转录调节因子1(ASXL1)基因突变率、染色质重塑和转录调控基因功能组突变率、3种预后系统积分比较,差异有统计学意义(P<0.05),邪热炽盛、毒瘀阻滞证组转录调控基因功能组突变率和3种预后系统积分均高于其他两组(P<0.05)。在3个预后积分系统的较高危组中,邪热炽盛、毒瘀阻滞证患者占比均高于其他两种证型。结论:MDS病机以虚为本,临床患者以虚实夹杂证多见;邪热炽盛、毒瘀阻滞证预后较差,推测其机制可能与ASXL1基因突变、7号染色体的完全丢失和其长臂的部分缺失(-7/7q-)等遗传学情况相关。

Objective:To explore the correlation among traditional Chinese medicine(TCM)syndrome types,molecular biology,cytogenetics and prognosis in patients with myelodysplastic syndrome(MDS).Methods:The statistical methods of nonparametric rank sum test or chi-square test were used to retrospectively analyze the TCM syndrome types,peripheral blood indicators,disease classification,molecular biology,cytogenetics,prognosis of 85 newly diagnosed MDS patients and to discuss the correlation between TCM syndrome types and the latter factors.Results:The TCM syndrome types of the 85 patients with MDS were mainly qi-yin deficiency and toxin-stasis obstruction syndrome,followed by spleen and kidney deficiency and toxin-stasis obstruction syndrome,and pathogenic heat exuberance and toxin-stasis obstruction syndrome.The level of absolute neutrophil coun(t ANC)in patients with pathogenic heat exuberance and toxin-stasis obstruction syndrome was significantly lower than that in patients with spleen and kidney deficiency and toxin-stasis obstruction syndrome(P<0.01).The level of hemoglobin(HGB)in patients with qi-yin deficiency and toxin-stasis obstruction syndrome was significantly lower than that in patients with spleen and kidney deficiency and toxin-stasis obstruction syndrome(P<0.001).The difference in the distribution of disease types among the three syndrome types was statistically significant(P<0.05).All patients with pathogenic heat exuberance and toxin-stasis obstruction syndrome had a disease classification of excess blasts of primitive cell(EB type).The differences in mutation rate of transcription regulator 1(ASXL1)gene,the mutation rate of chromatin remodeling and transcription regulation gene function group,and the scores of three prognostic scoring systems among the three syndrome types were statistically significant(P<0.05).The mutation rate of transcription regulation gene function group and the scores of three prognostic scoring systems in the pathogenic heat exuberance and toxin-stasis obstruction syndrome group were higher than those in the other two groups(P<0.05).In the higher-risk categories of the three prognostic scoring systems,patients with pathogenic heat exuberance and toxin-stasis obstruction syndrome had a higher proportion than those with the other two syndrome types.Conclusions:The pathogenesis of MDS is primarily based on deficiency,and clinically,patients often present with mixed deficiency and excess syndrome types.The prognosis of pathogenic heat exuberance and toxin-stasis obstruction syndrome is poor,and it is speculated that the mechanism may be related to genetic conditions such as ASXL1 gene mutation,complete loss of chromosome 7,and partial deletion of its long arm(-7/7q-).