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急性白血病患者骨髓中细胞间粘附分子-3的表达与临床关系的研究
Study of the Expression of Inter-cellular Adhesion Molecule-3 in Bone Marrow and Its Clinical Significances in Patients with Acute Leukemia
【作者】 陈玲;
【作者基本信息】 山东大学 , 内科学, 2008, 硕士
【摘要】 目的:细胞间粘附分子(inter-cellular adhesion molecules,I-CAMs)属于免疫球蛋白超家族粘附分子,涉及细胞-细胞粘附。目前许多研究发现I-CAMs在白血病、淋巴瘤、骨髓瘤等恶性血液病患者中高水平表达,可能在恶性血液病的发生、转移、评估预后中发挥着重要的作用。本文观察及探讨细胞间粘附分子-3(inter-cellularadhesion molecule-3,ICAM-3)在急性白血病(acute leukemia,AL)中的表达变化及其在白血病发生、临床疗效、髓外浸润中的意义。方法:1.研究对象2007年4月至11月在山东大学附属省立医院血液科收治的初发AL患者54例及正常对照10例。54例AL患者按不同标准分组①急性非淋巴细胞白血病患者(acute nonlymphoblastic leukemia,ANLL)33例;急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)21例,包括B-ALL 14例,T-ALL 7例;②发生组织浸润者25例,无组织浸润者29例;③WBC≥100×10~9/L者10例,WBC<100×10~9/L者44例。2.研究方法采用免疫组织化学二步法,选择国际上公认的第一线单抗,ICAM-3抗体购于美国Labvision公司,应用生物素-亲和素-碱性磷酸酶法(ABC-AP)对54例初发AL患者治疗前后及10例正常对照骨髓单个核细胞ICAM-3的表达进行检测(玻片法)。3.统计学处理所有数据均用SPSS13.0统计软件分析。数据采用中位数、(?)±s、百分率表示,多组间均数比较采用方差分析,两组间均数比较采用t检验,两参数间的相关性采用Spearman等级检验。结果:1、化疗前各组ICAM-3的表达率与正常对照组比较,ANLL组与ALL组ICAM-3表达率显著升高,且ANLL组ICAM-3表达率与ALL组差异无统计学意义,T-ALL组与B-ALL组间化疗前ICAM-3表达率差异无统计学意义。2、ICAM-3表达率与AL患者临床特征的关系54例AL患者≤20岁组(n=7,89.30±4.98),21~40岁组(n=20,78.89±17.95),≥41岁组(n=27,76.20±20.65)。各年龄组间ICAM-3表达率差异无统计学意义(p>0.05);男性患者(n=33,84.36±12.91)与女性患者(n=21,74.64±22.19)化疗前ICAM-3表达率差异无统计学意义(p>0.05);通过Spearman等级检验,ICAM-3的表达与AL患者的就诊时Hb(r=0.18)及BPC(r=-0.126)等因素,显示无相关关系,而与化疗前骨髓原始细胞比例(r=0.467,P<0.01)呈正相关。同时外周血WBC≥100×10~9组比WBC<100×10~9组ICAM-3的表达率高,且WBC≥100×10~9组CR较低。3、化疗后未缓解组与缓解组、缓解组与正常对照组间ICAM-3的表达率的比较经过一个疗程的化疗后,ANLL、ALL缓解组ICAM-3的表达与对照组差异无统计学意义;未缓解组与缓解组ICAM-3表达率有显著差异,未缓解组的ICAM-3表达率明显高于缓解组。4、白血病浸润组与非浸润组ICAM-3的表达浸润组与非浸润组ICAM-3的表达有显著统计学意义(p<0.01),浸润组ICAM-3的表达高于非浸润组。结论:1.化疗前在急性白血病中ICAM-3的表达明显高于正常对照组,且经过一个疗程的化疗后,ANLL、ALL缓解组ICAM-3的表达与对照组差异无统计学意义;未缓解组与缓解组ICAM-3表达率有显著差异,未缓解组的ICAM-3表达率明显高于缓解组。其表达水平的高低可作为AL观察临床疗效及预后的指标之一。2.化疗前ICAM-3表达率与骨髓原始细胞比例呈正相关,这可能与肿瘤负荷有关。3.浸润组ICAM-3的表达高于非浸润组,提示急性白血病的组织浸润机制可能与细胞间粘附分子表达升高有关。
【Abstract】 ObjectiveInter-cellular adhesion molecules(I-CAMs)are immunoglobulin superfamily adhesion molecule,involved cell-cell adhesion.Many studies found that the patients of leukemia,lymphoma,myeloma and other hematologic malignancies with high level expression of I-CAMs.I-CAMs may play a key role in extramedullary infiltration,tumor metastasis and prognosis.To review the expressions of inter-cellular adhesion molecule-3(ICAM-3)in acute leukemia.To investigate the role of ICAM-3 in the clinical therapeutic efficacy and extramedullary infiltration.Methods1.Study To select 54 Newly Diagnosed patients with AL of receiving hospitalization and 10 healthy person from April 2007 to November 2006 in Department of Hematology,Provincial Hospital Affiliated to Shandong University.54 AL patients were parted by different standards:①33 acute nonlymphoblasfic leukemia (ANLL)patients,21 acute lymphoblasfic leukemia(ALL)patients,including 14 B-ALL patients and 7 T-ALL patients.②25 extramedullary infiltration patients,29 non-extramedullary infiltration patients.③10 WBC≥100×10~9/L patients,44 WBC<100×10~9/L patients.2.Methoder The expressions of ICAM-3 of 54 AL patients and 10 normal controls were detected by bone marrow smear immunohistochemistry.3.Statistics All data were analyzed by statistical software SPSS13.0.Date using median,(?)±s and percentages.To compare Multi-group by analysis of variance.To compare two groups by T-test.Two parameters using the Spearman rank correlation test.Results1.The expressions of ICAM-3 before therapy The expressions of ICAM-3 in AL patients were significantly higher than that in the controls,but has no difference between ANLL and ALL,also has no difference between T-ALL and B-ALL.2.The relationship betwwen ICAM-3 and the clinical features of patients All 54 patients,≤20 age group(n =7,89.30±=4.98),21~40 age group(n =20, 78.89±17.95),≥41 age group(n =27,76.20±20.65).There was no significant difference of the ratio among three age groups.The expressions of ICAM-3 had no correlation with patients’ age,gender,Hb and BPC,but there were direct correlation with the ratio of primitive bone marrow cells;The expressions of ICAM-3 in patients whose WBC≥100×10~9/L were higher than that in the patients whose WBC<100×10~9/L(P<0.05).3.The expressions of ICAM-3 in AL patients without complete remission(CR) were much higher than the patients with CR(P<0.01).The patients with CR had no difference with that of the controls(P>0.05);4.The expressions of ICAM-3 were much higher in leukemic cells with extramedullary infiltration than leukemic cells without extramedullary infiltration(P<0.01).Conclusions 1.The expressions of ICAM-3 in AL were significantly higher than that in the controls.;The expressions of ICAM-3 in AL patients without complete remission(CR) were much higher than the patients with CR(P<0.01).The patients with CR had no difference with that of the controls(P>0.05);They could be used as helpful markers to observe therapeutic efficacy and to judge prognosis.2.The expressions of ICAM-3 were positively correlated with the percentages of primitive bone marrow cells.3.The expressions of ICAM-3 in AL were significantly higher than that in the controls.They might be correlated with infiltration of acute leukemic cell.
【Key words】 Inter-cellular adhesion molecule-3; acute leukemia; Extramedullary infiltration;