急性髓细胞白血病患儿骨髓自分泌运动因子受体表达及其预后意义

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目的糖蛋白AMFR(autocrine motility factor receptor)是自分泌运动因子(autocrine motility factor,AMF)的天然受体,AMFR与AMF结合后能促使细胞的运动、迁移。通过对急性髓细胞白血病(acute myelocytic leukemia,AML)患儿骨髓液单个核细胞AMFR表达情况的检测,探讨AMFR对患者预后的影响。方法选取2011-12-01-2013-12-31郑州大学第一附属医院儿科住院的初治核型正常的AML 35例患儿作为初治组,选取同期住院排除恶性疾病的儿童30例作为对照组;采用实时定量PCR、蛋白质印记法检测初治组与对照组儿童骨髓单个核细胞中AMFR mRNA和蛋白的相对表达量,按AMFR mRNA二分位切点将初治组分为高表达组和低表达组,Kaplan-Meier法分析两组2年的总生存时间;Cox回归模型单因素和多因素分析AMFR表达水平、年龄、性别、外周血白细胞数目、骨髓原始细胞比例等因素与预后的相关性。结果初治组按标准化疗方案进行规律化疗,根据治疗效果可分为缓解组(n=19)与复发组(n=16)。初治组、缓解组、复发组与对照组AMFR mRNA的相对表达量分别为(0.61±0.11)、(0.38±0.07)、(0.86±0.12)与(0.19±0.02),各组之间两两比较,差异均有统计学意义,P<0.001。初治组AMFR蛋白的相对表达量为(0.55±0.12),缓解组为0.28±0.07,复发组为0.72±0.13,对照组为0.14±0.06,各组之间两两比较,差异均有统计学意义,P<0.001。采用Kaplan-Meier分析,AMFR低表达组中位生存期为710d(95%CI为116.409~245.251),高于AMFR高表达组的69d(95%CI为14.424~123.576),经Log-Rank统计分析,两组之间的总体生存率(OS)差异有统计学意义,P=0.003。采用Cox回归模型纠正性别、年龄、外周血白细胞数、骨髓原始细胞比例和白血病FAB分型等因素,AMFR基因mRNA表达水平和白细胞数是影响AML不良预后的因素。结论 AMFR在AML中存在高表达,其表达水平越高,临床预后越差。 Objective AMFR (autocrine motility factor receptor) is a natural receptor of autocrine motility factor (AMF). AMFR and AMF can promote the movement and migration of cells. AMFR expression in bone marrow mononuclear cells from children with acute myelocytic leukemia (AML) was measured to investigate the effect of AMFR on the prognosis of patients. Methods 2011-12-01-2013-12-31 Zhengzhou Children’s Hospital of the First Affiliated Hospital of children with first-onset karyotypic AML 35 cases as a naive group, select the same period hospitalized patients with malignant disease in 30 cases as a control Group. The relative expression of AMFR mRNA and protein in bone marrow mononuclear cells of newly diagnosed and control children was detected by real-time quantitative PCR and Western blotting. According to AMFR mRNA dichotomous cut point, the naive group was divided into high expression group and low The Kaplan-Meier method was used to analyze the 2-year overall survival time. Cox regression model was used to analyze the correlation between AMFR expression level, age, sex, peripheral blood leukocyte count, bone marrow blast cell count and prognosis . The results of the initial treatment group according to the standard chemotherapy regimen of regular chemotherapy, according to the treatment effect can be divided into remission group (n = 19) and recurrence group (n = 16). The relative expression levels of AMFR mRNA in the newly diagnosed group, remissioned group, relapsed group and control group were (0.61 ± 0.11), (0.38 ± 0.07), (0.86 ± 0.12) and (0.19 ± 0.02) Comparison, the differences were statistically significant, P <0.001. The relative expression of AMFR protein was (0.55 ± 0.12) in initial treatment group, 0.28 ± 0.07 in remission group, 0.72 ± 0.13 in recurrence group and 0.14 ± 0.06 in control group, with statistical significance Significance, P <0.001. Kaplan-Meier analysis showed that the median survival time of AMFR low expression group was 710d (95% CI: 116.409-245.251), which was higher than that of AMFR high expression group (69.4% -14.424 ~ 123.576) There was a statistically significant difference in overall survival (OS) between the two groups, P = 0.003. Cox regression model was used to correct the gender, age, peripheral blood leukocytes, bone marrow blasts and FAB genotype of leukemia. AMFR mRNA expression and leucocyte count were the factors affecting the poor prognosis of AML. Conclusion AMFR is highly expressed in AML. The higher the expression level, the worse the clinical prognosis.
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