急性淋巴细胞白血病患者FGFR3表达对循环内皮细胞增殖的影响  

Expression of FGFR3 in acute lymphoblastic leukemia patients and its contribution to proliferation of circulating endothelial cells

作　　者：吴静怡[1] 周剑峰[2] 裴仁治[1] 张丕胜[1] 刘旭辉[1] 杜小红[1] 

机构地区：[1]宁波大学医学院附属鄞州医院血液科,浙江宁波315000 [2]华中科技大学同济医学院同济医院血液科,湖北武汉430030

出　　处：《中国病理生理杂志》2017年第4期694-698,共5页Chinese Journal of Pathophysiology

基　　金：浙江省自然科学基金资助项目(No.LQ12H08001);浙江省卫生厅一般研究项目资助(No.201235256);宁波市自然科学基金资助项目(No.2012A610236);宁波市医学科技计划资助项目(No.2011B23)

摘　　要：目的:了解急性淋巴细胞白血病(ALL)患者成纤维细胞生长因子受体3(FGFR3)表达对循环内皮细胞(CECs)增殖的影响。方法:通过RT-PCR法检测44例ALL患者骨髓中FGFR3 mRNA表达,分成FGFR3^+组及FGFR3^-组进行Kaplan-Meier生存分析。利用免疫磁珠结合流式细胞术分离计数CECs,对比两组CECs数量、表面抗原表达、生长曲线及集落生成数的差异。免疫荧光组化染色测定CECs表面FGFR3表达水平。结果:44例核型正常ALL患者中FGFR3 mRNA表达阳性率为43.2%,T-ALL组的FGFR3表达高于B-ALL组(P<0.05)。19 d骨髓原始细胞比例≥5%的患者FGFR3表达升高(P<0.05)。FGFR3阳性组的总生存率明显低于阴性组(P<0.05)。分离出的CECs高表达CD31、CD144、VEGFR-2和CD146,基本不表达CD45。与FGFR3阴性组相比,阳性组CECs数量、CD133的阳性率及集落生成数均增多(P<0.05)。体外培养中,FGFR3阳性组与阴性组相比,生长曲线3个时点上的细胞数差异有统计学显著性(P<0.05)。19例ALL-FGFR3^+患者CECs表面均能检测到FGFR3表达,阳性率为29.00%±15.71%。结论:致癌基因FGFR3对ALL患者CECs的增殖有促进作用,可能具备了抗肿瘤及抗血管生成的双重靶点身份,可以为今后的分子治疗提供更多的选择。AIM： To evaluate the expression of fibroblast growth factor receptor 3（ FGFR3） in acute lymphocytic leukemia（ ALL） patients and its contribution to the proliferation of circulating endothelial cells（ CECs）.METHODS： The mRNA expression levels of FGFR3 in 44 patients with ALL were assayed by RT-PCR. Overall survival（ OS） rates of the patients in FGFR3＋ group and FGFR3- group were estimated by Kaplan-Meier analysis. The CECs were sorted from peripheral blood by magnetic-activated cell sorting and then counted by 3-color flow cytometry. The cell counts,antigen expression,growth curve and colony forming rate of the CECs in the 2 groups were determined. The FGFR3 expression of CECs was identified by immunofluorescence staining. RESULTS： The positive rate of FGFR3 mRNA expression was 43. 2% in 44 ALL patients with normal karyotype. T-ALL expressed higher level of FGFR3 than B-ALL（ P〈0. 05）.FGFR3 was over-expressed in ALL patients with bone marrow blast proportion ≥5%（ P〈0. 05）. The probability of OS was significantly lower in FGFR3＋ group than that in FGFR3- group（ P〈0. 05）. The sorted CECs highly expressed CD31,CD144,VEGFR-2 and CD146,and rarely expressed CD45. The counts of CECs and expression level of CD133 significantly increased in FGFR3＋ group compared with FGFR3- group. The same result of the amount of colony formation was observed（ P〈0. 05）. There was significant difference at 3 time points of cultured CECs count in vitro between FGFR3＋ group and FGFR3- group（ P〈0. 05）. The positive rate of FGFR3 expression of CECs from 19 ALL-FGFR3＋ patients was（ 29. 00 ± 15. 71） %. CONCLUSION： The over-expression of FGFR3 gene in ALL may be helpful to evaluate the proliferation of CECs,and become a double target with anti-tumor and anti-angiogenesis effects to offer more choice for molecular therapy in the future.

关 键 词：急性淋巴细胞白血病 成纤维细胞生长因子受体3 循环内皮细胞 

分 类 号：R730.23[医药卫生—肿瘤] R733.71[医药卫生—临床医学]