四色流式细胞术分析多发性骨髓瘤的免疫表型与临床特征及预后关系

张丽娜; 谢晓宝; 邱国强; 吴浩清; 王志林

doi:10.13201/j.issn.1004-2806.2012.04.008

四色流式细胞术分析多发性骨髓瘤的免疫表型与临床特征及预后关系

- 苏州大学附属第三医院血液科(江苏常州, 213003)

详细信息

通讯作者: 谢晓宝,E-mail:czxxb1098@163.com

中图分类号: R554

收稿日期: 2011-09-15

Four-color flow cytometric analysis of multiple myeloma and the correlation with its clinical features and prognosis

- Department of Hematology, Third Hospital of Suzhou University, Changzhou, 213003, China

More Information

Corresponding author: XIE Xiaobao, E-mail: czxxb1098@163.com

Received Date: 15 September 2011

摘要

摘要: 目的:利用四色流式术探讨多发性骨髓瘤(MM)免疫表型与临床特征的相关性及其预后价值。方法:分别用四色流式细胞术、间期荧光原位杂交技术检测50例初诊MM患者的瘤细胞表面免疫表型以及细胞遗传学异常,并收集患者的临床和实验室指标。结果:共检测不同组合的四色CD抗原:CD38-PE/CD45-Percp/CD19-FITC/CD56-APC;CD38-FITC/CD138-Percp/CD117-PE/CD28-APC;CD38-PE/CD138-Percp/CD27-APC/CD20-FITC,其中CD28的表达多与ISS高分期相关,多易骨髓浸润,出现贫血、高钙、肾功能损害、低白蛋白、β₂-微球蛋白高水平,以及IGH易位等不良预后因素,而CD117则为较佳预后因素,其表达缺失患者多易出现骨髓浸润,低白蛋白,且易出现del(13q14),IGH易位,进一步分析发现del(13q14)与IGH易位之间存在相关性(r=0.378,P<0.05);分别根据CD28和CD117的联合表达以及FISH预后风险分组,流式高危组(CD28⁺CD117^-)与FISH预后风险分组中的高危组(13q14缺失)之间差异有统计学意义(P<0.05)。结论:CD28和CD117对MM患者的临床预后具有重要的价值,且其联合评估能够帮助MM患者识别预后因素,指导临床治疗。
- 多发性骨髓瘤 /
- 流式细胞术 /
- 免疫表型 /
- 临床特征 /
- 预后
Abstract: Objective:This study was purposed to investigate the relation between the immunophenotype and clinical features or prognosis in multiple myeloma (MM).Method:The immunophenotype and cytogenetic abnormalities of myeloma cell of 50 cases of newly diagnosed MM patients were detected with multiparameter flow cytometry (MFC) and interphase fluorescence in situ hybridization (I-FISH)respectively.The clinical and laboratory parameters of the patients were colleted and analyzed as well.Result:In this study,different antigen combinations were detected: CD38-PE/CD45-Percp/CD19-FITC/CD56-APC,CD38-FITC/CD138-Percp/CD117-PE/CD28-APC,CD38-PE/CD-138-Percp/CD27-APC/CD20-FITC.Expression of CD28 was associated with a significant higher frequency of advanced International staging system (ISS) stages,higher levels of BM infiltration (PC≥30%)and β₂-microglobulin(β₂-MG≥0.2 g/L),greater frequencies of anemia (Hemoglobin≤100 g/L),hypercalcemia(calcium≥2.75 mmol/L),renal impairment (creatinine≥0.2 g/L),low albumin(albumin≤30 g/L),and IGH translocations .In turn,lack of CD117 expression was associated with higher levels of BM infiltration,greater frequencies of low albumin,del(13q14) and IgH translocations.Further analysis revealed that there was correlation between del (13q14) and IGH translocation(r=0.378,P<0.05).Grouped according to the joint expression of CD28 and CD117 or the risk stratification of FISH,we found that there was significant difference between the CD28⁺CD117^- group and del(13q14) group(P<0.05).Conclusion:The expression of CD28 and CD117 has important clinical prognosis value for MM patients,which helps for identifying the prognostic factors and guiding clinical treatment in MM.
- multiple myeloma /
- multiparameter flow cytometry /
- immunophenotype /
- clinical features /
- prognosis

HTML全文

参考文献(21)

[1]	郝玉书,王建祥,肖志坚.白细胞疾病基础理论与临床[M].上海:上海科学技术出版社,2006:711-738.
[2]	[KG*1]张之南,沈悌.血液病诊断及疗效标准[M].3版.北京:科学出版社,2007:232-235.
[3]	[KG*1]MATEO G,MONTALBAN M A,VIDRIALES M B,et al.Prognostic value of immunophenotyping in multiple myeloma: a study by the PETHEMA/GEM cooperative study groups on patients uniformly treated with high-dose therapy[J].J Clin Oncol,2008,26: 2737-2744.
[4]	[KG*1]DISPENZIERI A,RAJKUMAR S V,GERTZ M A,et al.Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement[J].Mayo Clin Proc,2007,82: 323-341.
[5]	[KG*1]RAWSTRON A C,DAVIES F E,DASGUPTA R,et al.Flow cytometric disease monitoring in multiple myeloma: the relationship between normal and neoplastic plasma cells predicts outcome after transplantation[J].Blood,2002,100: 3095-3100.
[6]	[KG*1]RAWSTRON A C,ORFAO A,BEKSAC M,et al.Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders[J].Haematologica,2008,93: 431-438.
[7]	[KG*1]陈葆国,罗文达,李伯利,等.多发性骨髓瘤流式细胞术免疫表型及微量残留病研究[J].中华检验医学杂志,2011,34(1):10-14.
[8]	[KG*1]CAO W,GOOLSBY C L,NENLSON B P,et al.Instability of immunophenotype in plasma cell myeloma[J].Am J Clin Pathol,2008,129: 926-933.
[9]	[KG*1]KUMAR S,KIMLINGER T,MORICE W.Immunophenotyping in multiple myeloma and related plasma cell disorders[J].Best Pract Res Clin Haematol,2010,23: 433-451.
[10]	PAIVA B,ALMEIDA J,PEREZ-ANDRES M,et al.Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders[J].Cytometry B Clin Cytom,2010,78: 239-252.
[11]	RAJA K R,KOVAROVA L,HAJEK R.Review of phenotypic markers used in flow cytometric analysis of MGUS and MM,and applicability of flow cytometry in other plasma cell disorders[J].Br J Haematol,2010,149: 334-351.
[12]	GUPTA R,BHASKAR A,KUMAR L,et al.Flow cytometric immunophenotyping and minimal residual disease analysis in multiple myeloma[J].Am J Clin Pathol,2009,132: 728-732.
[13]	BAHLIS N J,KING A M,KOLONIAS D,et al.CD28-mediated regulation of multiple myeloma cell proliferation and survival[J].Blood,2007,109: 5002-5010.
[14]	TRCIC R L,SKELIN I K,SUSTERCIC D,et al.Cytogenetics of multiple myeloma[J].Coll Antropol,2010,34:41-44.
[15]	SHAPIRO V S,MOLLENAUER M N,WEISS A.Endogenous CD28 expressed on myeloma cells up-regulatesinterleukin-8 production: implications for multiple myeloma progression[J].Blood,2001,98: 187-193.
[16]	MATEO G,MONTALBAN M A,VIDRIALES M B,et al.Prognostic value of immunophenotyping in multiple myeloma: a study by the PETHEMA/GEM cooperative study groups on patients uniformly treated with high-dose therapy[J].J Clin Oncol,2008,26: 2737-2744.
[17]	KRAJ M,POGLOD R,KOPEC-SZLEZAK J,et al.C-kit receptor (CD117) expression on plasma cells in monoclonal gammopathies[J].Leuk Lymphoma,2004,45: 2281-2289.
[18]	PRUNERI G,PONZONI M,FERRERI A J,et al.The prevalence and clinical implications of c-kit expression in plasma cell myeloma[J].Histopathology,2006,48: 529-535.
[19]	BATAILLE R,PELLAT-DECEUNYNCK C,ROBILLARD N,et al.CD117(c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis[J].Leuk Res,2008,32: 379-382.
[20]	MATEO G,CASTELLANOS M,RASILLO A,et al.Genetic abnormalities and patterns of antigenic expression in multiple myeloma[J].Clin Cancer Res,2005,11: 3661-3667.
[21]	GUTIERREZ N C,CASTELLANOS M V,MARTIN M L,et al.Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor,whereas RB deletion as a unique abnormality is not associated with adverse prognosis[J].Leukemia,2007,21: 143-150.