本文關(guān)鍵詞：CD47在急性髓細(xì)胞白血病中的表達(dá)及其療效預(yù)后的關(guān)系　出處：《河北醫(yī)科大學(xué)》2015年碩士論文　論文類(lèi)型：學(xué)位論文

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【摘要】：目的:CD47,又稱(chēng)為整合素相關(guān)蛋白(integrin-associated protein,IAP),是一種廣泛表達(dá)于多種細(xì)胞表面的跨膜糖蛋白,參與到人體內(nèi)的多個(gè)生理學(xué)過(guò)程中,其中包括細(xì)胞遷移,T細(xì)胞及樹(shù)突狀細(xì)胞活化,軸突的生長(zhǎng)。其與整合素配體、信號(hào)調(diào)節(jié)蛋白α(signal regulatory proteinαSIRP-α)、凝血酶敏感蛋白(TSP-1)相結(jié)合,在炎癥反應(yīng)、免疫應(yīng)答、腫瘤免疫等方面發(fā)揮重要的作用。本文旨在研究CD47在AML中的表達(dá)、該數(shù)值與疾病髓外浸潤(rùn)、復(fù)發(fā)及其在預(yù)測(cè)疾病預(yù)后方面的臨床意義。方法:應(yīng)用流式細(xì)胞儀檢測(cè)了136例初治急性髓細(xì)胞白血病(除外急性早幼粒細(xì)胞白血病,包括M0 7例,M1 15例,M2 39例,M4 20例,M5 41例,M6 14例)患者骨髓白血病細(xì)胞中CD47的表達(dá)。對(duì)其中126例AML患者進(jìn)行跟蹤隨訪,分析白血病細(xì)胞表達(dá)CD47陽(yáng)性和陰性對(duì)AML預(yù)后的影響;所取病例進(jìn)行分組:其中有肝、脾、淋巴結(jié)腫大者49例,無(wú)肝、脾、淋巴結(jié)腫大者87例;白細(xì)胞≥20×109/L者80例,白細(xì)胞20×109/L者56例,分析其對(duì)AML預(yù)后的影響。所有病例均行血常規(guī)、血細(xì)胞分類(lèi)、骨髓形態(tài)、染色體核型分析、白血病相關(guān)融合基因檢測(cè)、流式免疫表型,結(jié)合相關(guān)癥狀、臨床體征予以診斷。初診AML患者骨髓原始細(xì)胞占34%~95%,采用IDA(去甲氧柔紅霉素+阿糖胞苷)、MAC(米托蒽醌+阿糖胞苷+環(huán)磷酰胺)、DA(柔紅霉素+阿糖胞苷)為主的方案進(jìn)行誘導(dǎo)分化化療。同時(shí)選取了18例來(lái)自良性血液病(包括營(yíng)養(yǎng)性巨幼細(xì)胞性貧血6例,缺鐵性貧血7例,再生障礙性貧血5例)的患者作為對(duì)照組,檢測(cè)其骨髓中CD47的表達(dá)。結(jié)果:對(duì)照組18例患者骨髓中CD47表達(dá)陽(yáng)性3例(16.67%),136例AML患者中,男性75例,女性61例,年齡波動(dòng)于14~75歲,其中白血病細(xì)胞表達(dá)CD47陽(yáng)性103例(75.74%),明顯高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(X2=25.85,P0.01)。對(duì)126例AML進(jìn)行1~26個(gè)月跟蹤隨訪,結(jié)果顯示:98例CD47陽(yáng)性的AML患者1-2個(gè)療程正規(guī)化療后46例達(dá)完全緩解,完全緩解率為46.94%,47例復(fù)發(fā),復(fù)發(fā)率為47.96%,42例死亡,病死率為42.86%,28例CD47陰性的AML患者1-2個(gè)療程正規(guī)化療后20例達(dá)完全緩解,完全緩解率為71.43%,7例復(fù)發(fā),復(fù)發(fā)率為25.00%,5例死亡,病死率為17.86%,三者差異有統(tǒng)計(jì)學(xué)意義(X2值分別為5.24,4.69,5.82,P均0.05)。對(duì)AML患者進(jìn)行平均生存時(shí)間分析,結(jié)果顯示,CD47表達(dá)陽(yáng)性為16.99±1.15個(gè)月,而CD47表達(dá)陰性為21.90±1.866個(gè)月,比較兩者之間的差異存在統(tǒng)計(jì)學(xué)方面的意義(P0.05)。AML各亞型骨髓白血病細(xì)胞上的CD47表達(dá)差異不明顯(P0.05)。AML表面CD47表達(dá)增加者的總生存率往往降低。在AML中,CD47表達(dá)增加可以作為不良預(yù)后因素之一。研究表明,AML患者的CD47表達(dá)水平明顯增加,而其他來(lái)自良性血液病的對(duì)照組,包括營(yíng)養(yǎng)性巨幼細(xì)胞性貧血、缺鐵性貧血、再生障礙性貧血骨髓細(xì)胞的CD47表達(dá)未見(jiàn)增加。骨髓白血病細(xì)胞表面的CD47表達(dá)水平與AML患者的MICM分型或FAB無(wú)關(guān),某些核型異常但臨床預(yù)后較好的患者骨髓白血病細(xì)胞表面CD47表達(dá)水平較低,如t(8;21)(q22;q22),而在1/3正常核型及FLT-ITD突變的患者骨髓白血病細(xì)胞CD47表達(dá)水平較高。本次實(shí)驗(yàn)結(jié)果證實(shí),AML患者的年齡、性別、原始細(xì)胞的數(shù)量與CD47是否陽(yáng)性表達(dá)無(wú)相關(guān)性(P0.05),入組的136例AML中有肝、脾、淋巴結(jié)腫大49例,CD47陽(yáng)性表達(dá)者46例(93.88%),無(wú)肝、脾、淋巴結(jié)腫大者87例,CD47表達(dá)陽(yáng)性者57例(65.52%),差異有統(tǒng)計(jì)學(xué)意義(X2=13.72,P0.01)。提示,肝脾淋巴結(jié)腫大易出現(xiàn)在CD47過(guò)表達(dá)的AML患者。以白細(xì)胞數(shù)20.0×109/L為界限將136例AML患者分為兩組,外周血白細(xì)胞≥20.0×109/L的80例,其中CD47表達(dá)陽(yáng)性者68例(85.00%),外周血白細(xì)胞20.0×109/L的56例,其中CD47表達(dá)陽(yáng)性者35例(62.50%),差異有統(tǒng)計(jì)學(xué)意義(X2=9.08,P0.05)。結(jié)果顯示,高白細(xì)胞的AML患者CD47表達(dá)陽(yáng)性率高。結(jié)論:急性髓細(xì)胞白血病CD47表達(dá)陽(yáng)性的患者緩解率低,易復(fù)發(fā)、病死率高、生存時(shí)間短。CD47在急性髓細(xì)胞白血病細(xì)胞上表達(dá)或可作為判斷AML療效和預(yù)后的指標(biāo)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(zhèn)ｈ，

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