CD47在急性髓细胞白血病中的表达及其疗效预后的关系

发布时间：2018-01-11 07:27

  本文关键词：CD47在急性髓细胞白血病中的表达及其疗效预后的关系　出处：《河北医科大学》2015年硕士论文　论文类型：学位论文

  更多相关文章： 急性髓细胞白血病 CD47 预后 浸润 复发

【摘要】：目的:CD47,又称为整合素相关蛋白(integrin-associated protein,IAP),是一种广泛表达于多种细胞表面的跨膜糖蛋白,参与到人体内的多个生理学过程中,其中包括细胞迁移,T细胞及树突状细胞活化,轴突的生长。其与整合素配体、信号调节蛋白α(signal regulatory proteinαSIRP-α)、凝血酶敏感蛋白(TSP-1)相结合,在炎症反应、免疫应答、肿瘤免疫等方面发挥重要的作用。本文旨在研究CD47在AML中的表达、该数值与疾病髓外浸润、复发及其在预测疾病预后方面的临床意义。方法:应用流式细胞仪检测了136例初治急性髓细胞白血病(除外急性早幼粒细胞白血病,包括M0 7例,M1 15例,M2 39例,M4 20例,M5 41例,M6 14例)患者骨髓白血病细胞中CD47的表达。对其中126例AML患者进行跟踪随访,分析白血病细胞表达CD47阳性和阴性对AML预后的影响;所取病例进行分组:其中有肝、脾、淋巴结肿大者49例,无肝、脾、淋巴结肿大者87例;白细胞≥20×109/L者80例,白细胞20×109/L者56例,分析其对AML预后的影响。所有病例均行血常规、血细胞分类、骨髓形态、染色体核型分析、白血病相关融合基因检测、流式免疫表型,结合相关症状、临床体征予以诊断。初诊AML患者骨髓原始细胞占34%~95%,采用IDA(去甲氧柔红霉素+阿糖胞苷)、MAC(米托蒽醌+阿糖胞苷+环磷酰胺)、DA(柔红霉素+阿糖胞苷)为主的方案进行诱导分化化疗。同时选取了18例来自良性血液病(包括营养性巨幼细胞性贫血6例,缺铁性贫血7例,再生障碍性贫血5例)的患者作为对照组,检测其骨髓中CD47的表达。结果:对照组18例患者骨髓中CD47表达阳性3例(16.67%),136例AML患者中,男性75例,女性61例,年龄波动于14~75岁,其中白血病细胞表达CD47阳性103例(75.74%),明显高于对照组,差异有统计学意义(X2=25.85,P0.01)。对126例AML进行1~26个月跟踪随访,结果显示:98例CD47阳性的AML患者1-2个疗程正规化疗后46例达完全缓解,完全缓解率为46.94%,47例复发,复发率为47.96%,42例死亡,病死率为42.86%,28例CD47阴性的AML患者1-2个疗程正规化疗后20例达完全缓解,完全缓解率为71.43%,7例复发,复发率为25.00%,5例死亡,病死率为17.86%,三者差异有统计学意义(X2值分别为5.24,4.69,5.82,P均0.05)。对AML患者进行平均生存时间分析,结果显示,CD47表达阳性为16.99±1.15个月,而CD47表达阴性为21.90±1.866个月,比较两者之间的差异存在统计学方面的意义(P0.05)。AML各亚型骨髓白血病细胞上的CD47表达差异不明显(P0.05)。AML表面CD47表达增加者的总生存率往往降低。在AML中,CD47表达增加可以作为不良预后因素之一。研究表明,AML患者的CD47表达水平明显增加,而其他来自良性血液病的对照组,包括营养性巨幼细胞性贫血、缺铁性贫血、再生障碍性贫血骨髓细胞的CD47表达未见增加。骨髓白血病细胞表面的CD47表达水平与AML患者的MICM分型或FAB无关,某些核型异常但临床预后较好的患者骨髓白血病细胞表面CD47表达水平较低,如t(8;21)(q22;q22),而在1/3正常核型及FLT-ITD突变的患者骨髓白血病细胞CD47表达水平较高。本次实验结果证实,AML患者的年龄、性别、原始细胞的数量与CD47是否阳性表达无相关性(P0.05),入组的136例AML中有肝、脾、淋巴结肿大49例,CD47阳性表达者46例(93.88%),无肝、脾、淋巴结肿大者87例,CD47表达阳性者57例(65.52%),差异有统计学意义(X2=13.72,P0.01)。提示,肝脾淋巴结肿大易出现在CD47过表达的AML患者。以白细胞数20.0×109/L为界限将136例AML患者分为两组,外周血白细胞≥20.0×109/L的80例,其中CD47表达阳性者68例(85.00%),外周血白细胞20.0×109/L的56例,其中CD47表达阳性者35例(62.50%),差异有统计学意义(X2=9.08,P0.05)。结果显示,高白细胞的AML患者CD47表达阳性率高。结论:急性髓细胞白血病CD47表达阳性的患者缓解率低,易复发、病死率高、生存时间短。CD47在急性髓细胞白血病细胞上表达或可作为判断AML疗效和预后的指标之一。
[Abstract]:Objective: CD47, also known as integrin associated protein (integrin-associated, protein, IAP) is a transmembrane glycoprotein widely expressed on the surface of various cells, participate in a number of human body physiology to the learning process, including cell migration, T cells and dendritic cell activation, axon growth and the integrin ligand. Signal regulated protein (signal alpha, regulatory protein alpha SIRP- alpha), thrombin sensitive protein (TSP-1) combined in inflammation, immune response, play an important role in tumor immunity and so on. This paper aims to study the expression of CD47 in AML, the numerical disease and extramedullary infiltration, recurrence and clinical significance in predicting the prognosis of the disease. Methods: detected 136 cases of newly diagnosed acute myeloid leukemia by flow cytometry (except for acute promyelocytic leukemia, including M0 7 cases, M1 15 cases, M2 39 cases, M4 20 cases, M5 41 cases, M6 14 cases) patients The expression of CD47 in bone marrow cells of leukemia. Of which 126 cases AML patients were followed up, the analysis of leukemia cells showed CD47 positive and negative influence on the prognosis of AML; the patients group: including liver, spleen, lymph nodes in 49 cases, liver, spleen, swollen lymph nodes in 87 cases; 80 cases of white blood cells over 20 * 109/L, 56 cases of white blood cells of 20 * 109/L, analyzes its influence on the prognosis of AML patients. All patients underwent routine blood test, blood cell classification, bone marrow morphology, karyotype analysis and detection of leukemia associated fusion gene, flow cytometry immunophenotyping, combined with related symptoms, clinical signs to diagnosis the bone marrow of patients with newly diagnosed AML. The original cells accounted for 34%~95%, using IDA (idarubicin and cytarabine), MAC (mitoxantrone + cytarabine + cyclophosphamide (DA), daunorubicin and cytarabine) based scheme for the differentiation of chemotherapy. At the same time selected 18 cases from benign Blood disease (including 6 cases of nutritional megaloblastic anemia of iron deficiency anemia in 7 cases, 5 cases of aplastic anemia) were used as control group, to detect the expression of CD47 in bone marrow. Results: in the control group, 18 cases of CD47 patients with bone marrow was found in 3 cases (16.67%), 136 cases of AML patients, male 75 cases, female 61 cases, age ranged from 14~75 years old, the expression of CD47 leukemia cells was positive in 103 cases (75.74%), significantly higher than the control group, the difference was statistically significant (X2=25.85, P0.01). In 126 cases of AML were 1~26 months of follow-up, the results showed: 98 cases of CD47 AML patients with positive 1-2 a course of chemotherapy after 46 cases of complete remission, complete remission rate was 46.94%, 47 cases of recurrence, the recurrence rate was 47.96%, 42 cases died, the mortality rate was 42.86%, 28 cases of CD47 negative AML patients 1-2 course standard chemotherapy for 20 cases of complete remission, complete remission rate was 71.43%, 7 cases of recurrence. The recurrence rate was 25%, 5 Cases died, the mortality rate was 17.86%, there was significant difference between the three groups (X2 = 5.24,4.69,5.82, P < 0.05). The average survival time of analysis, the results showed that for AML patients, the positive expression of CD47 was 16.99 + 1.15 months, while the negative expression of CD47 was 21.90 + 1.866 months, more than differences between the two there was the significance of (P0.05).AML subtypes of leukemia cells in the bone marrow on the expression of CD47 was no significant difference in overall survival (P0.05) expression of.AML CD47 increased the rate of surface tends to decrease. In AML, the increased expression of CD47 can be used as a prognostic factor. The study shows that the expression level of AML in patients with CD47 significantly increased, while the other from benign blood disease control group, including nutritional megaloblastic anemia, iron deficiency anemia, bone marrow cells of aplastic anemia. The expression of CD47 was not increased in leukemia cells in the bone marrow of the surface expression of CD47 and AM L鎮ｈ，

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