利用CD105和CD117建立双参数积分系统在MDS诊断中的应用
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摘要
目的:研究流式积分系统对骨髓增生异常综合征(MDS)诊断的价值。方法:回顾性分析了临床上进行免疫分型检测的130名MDS病人、19例健康对照以及89名病理对照中红系及幼稚细胞的表型,主要包括文献报道的四参数积分系统的4个参数,即髓系祖细胞相关的细胞群百分比、CD34~+细胞中B系祖细胞所占百分比、淋巴细胞与CD34~+髓系祖细胞CD45的比值,以及粒细胞与淋巴细胞SSC峰值比值;红系积分系统中的2个流式参数,即CD71和CD36平均荧光强度的变异系数,并进行积分分析。根据本组前期研究结果选取CD117~+CD105~-髓系祖细胞百分比以及CD105~+细胞在CD117~+细胞中的比例,建立双参数积分系统,并与四参数积分系统和红系积分系统进行比较。结果:四参数积分系统和红系积分系统对低危MDS诊断的敏感性分别为43.5%和63.0%,特异性分别为87.0%和63.9%。两个积分系统结合后,诊断低危MDS的敏感性为73.9%,特异性为62.0%。双参数积分系统诊断低危MDS的敏感性为76.1%,特异性为81.5%。通过与四参数积分系统结合,敏感性增加到78.3%,但特异性减低为71.3%;与红系积分系统结合后,虽然敏感性增加到87.0%,但特异性减低至54.6%。结论:单独利用双参数系统对低危MDS诊断可以取得较好的敏感性和特异性。
Objective: To study the value of flow cytometric scoring system in the diagnosis of myelodysplastic syndromes(MDS). Methods: The phenotypes of erythroid and immature cells were analyzed retrospectively in 130 MDS patients, 19 healthy controls and 89 pathological controls, all of them were well clinically immunophenotyped. The 4-parameter scoring system reported in the literature was studied, including myeloblast-related cluster size, B-progenitorrelated cluster size, lymphocyte to myeloblast CD45 ratio, and granulocyte to lymphocyte side scatter ratio. The two flow cytomatric parameters of the erythroid scoring system were analyzed, including CD36 coefficient of variation(CV) and CD71 CV. According to our previous study, the percentage of CD117~+CD105~-myeloid progenitor cells and the proportion of CD105~+ cells in CD117~+ cells were selected to establish a two-parameter scoring system, and compared with the fourparameter scoring system and the erythroid scoring system. Results: The sensitivity of the four-parameter scoring system and the erythroid scoring system for the diagnosis of low-risk MDS was 43.5% and 63.0%, and the specificity was 87.0% and 63.9%, respectively. After combining the two scoring systems, the sensitivity to diagnose low-risk MDS was 73.9% and the specificity was 62.0%. The sensitivity of the two-parameter scoring system for the diagnosis of low-risk MDS was 76.1% with a specificity of 81.5%. Combined with the four-parameter scoring system, the sensitivity was increased to 78.3%, but the specificity was reduced to 71.3%. After combining with the erythroid scoring system, the sensitivity reached 87.0%, but the specificity was reduced to 54.6%. Conclusion: Using the two-parameter scoring system alone can achieve great sensitivity and specificity in the diagnosis of low risk MDS.
Objective: To study the value of flow cytometric scoring system in the diagnosis of myelodysplastic syndromes(MDS). Methods: The phenotypes of erythroid and immature cells were analyzed retrospectively in 130 MDS patients, 19 healthy controls and 89 pathological controls, all of them were well clinically immunophenotyped. The 4-parameter scoring system reported in the literature was studied, including myeloblast-related cluster size, B-progenitorrelated cluster size, lymphocyte to myeloblast CD45 ratio, and granulocyte to lymphocyte side scatter ratio. The two flow cytomatric parameters of the erythroid scoring system were analyzed, including CD36 coefficient of variation(CV) and CD71 CV. According to our previous study, the percentage of CD117~+CD105~-myeloid progenitor cells and the proportion of CD105~+ cells in CD117~+ cells were selected to establish a two-parameter scoring system, and compared with the fourparameter scoring system and the erythroid scoring system. Results: The sensitivity of the four-parameter scoring system and the erythroid scoring system for the diagnosis of low-risk MDS was 43.5% and 63.0%, and the specificity was 87.0% and 63.9%, respectively. After combining the two scoring systems, the sensitivity to diagnose low-risk MDS was 73.9% and the specificity was 62.0%. The sensitivity of the two-parameter scoring system for the diagnosis of low-risk MDS was 76.1% with a specificity of 81.5%. Combined with the four-parameter scoring system, the sensitivity was increased to 78.3%, but the specificity was reduced to 71.3%. After combining with the erythroid scoring system, the sensitivity reached 87.0%, but the specificity was reduced to 54.6%. Conclusion: Using the two-parameter scoring system alone can achieve great sensitivity and specificity in the diagnosis of low risk MDS.
引文
1 Adès L,Itzykson R,Fenaux P.Myelodysplastic syndromes.Lancet,2014;383(9936):2239-2252.
2 Kern W,Haferlach C,Schnittger S,et al.Serial assessment of suspected myelodysplastic syndromes:significance of flow cytometric findings validated by cytomorphology,cytogenetics,and molecular genetics.Haematologica,2013;98(2):201-207.
3 Westers TM,Cremers EM,Oelschlaegel U,et al.Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes.Areport from the IMDSFlow working group.Haematologica,2017;102(2):308-319.
4 Westers TM,Ireland R,Kern W,et al.Standardization of flow cytometry in myelodysplastic syndromes:a report from an international consortium and the European LeukemiaNet Working Group.Leukemia,2012;26(7):1730-1741.
5 Wells DA,Benesch M,Loken MR,et al.Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation.Blood,2003;102(1):394-403.
6 Ogata K,Della Porta MG,Malcovati L,et al.Diagnostic utility of flow cytometry in low-grade myelodysplastic syndromes:a prospective validation study.Haematologica,2009;94(8):1066-1074.
7 Della Porta MG,Picone C,Pascutto C,et al.Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes:results of a European LeukemiaNET study.Haematologica,2012;97(8):1209-1217.
8 Bardet V,Wagner-Ballon O,Guy J,et al.Multicentric study underlining the interest of adding CD5,CD7 and CD56 expression assessment to the flow cytometric Ogata score in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.Haematologica,2015;100(4):472-478.
9 Cremers EMP,Westers TM,Alhan C,et al.Multiparameter flow cytometry is instrumental to distinguish myelodysplastic syndromes from non-neoplastic cytopenias.Eur J Cancer,2016;54:49-56.
10 Mathis S,Chapuis N,Debord C,et al.Flow cytometric detection of dyserythropoiesis:a sensitive and powerful diagnostic tool for myelodysplastic syndromes.Leukemia,2013;27(10):1981-1987.
11 Vardiman JW,Thiele J,Arber DA,et al.The 2008 revision of the World Health Organization(WHO)classification of myeloid neoplasms and acute leukemia:rationale and important changes.Blood,2009;114(5):937-951.
12 Cremers EM,Westers TM,Alhan C,et al.Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes.Haematologica,2017;102(2):320-326.
13 Lebrin F GM,Goumans MJ,Jonker L,et al.Endoglin promotes endothelial cell proliferation and TGF-b/ALK1 signal transduction.EMBO J,2004;23(20):4018-4028.
14 Gougos A St Jacgues S,Greaves A,et al.Identification of distinct epitopes of endoglin,an RGD-containing glycoprotein of endothelial cells,leukemic cells,and syncytiotrophoblasts.Int Immunol,1992;4(1):83-92.
15 Chen CZ,Li M,de Graaf D,et al.Identification of endoglin as a functional marker that defines long-term repopulating hematopoietic stem cells.Proc Natl Acad Sci U S A,2002;99(24):15468-15473.
16 Kapur NK,Morine KJ,Letarte M.Endoglin:a critical mediator of cardiovascular health.Vasc Health Risk Manag,2013;9:195-206.
17 Moody JL,Singbrant S,Karlsson G,et al.Endoglin is not critical for hematopoietic stem cell engraftment and reconstitution but regulates adult erythroid development.Stem Cells,2007;25(11):2809-2819.
18 Fajtova M,Kovarikova A,Svec P,et al.Immunophenotypic profile of nucleated erythroid progenitors during maturation in regenerating bone marrow.Leuk Lymphoma,2013;54(11):2523-2530.
2 Kern W,Haferlach C,Schnittger S,et al.Serial assessment of suspected myelodysplastic syndromes:significance of flow cytometric findings validated by cytomorphology,cytogenetics,and molecular genetics.Haematologica,2013;98(2):201-207.
3 Westers TM,Cremers EM,Oelschlaegel U,et al.Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes.Areport from the IMDSFlow working group.Haematologica,2017;102(2):308-319.
4 Westers TM,Ireland R,Kern W,et al.Standardization of flow cytometry in myelodysplastic syndromes:a report from an international consortium and the European LeukemiaNet Working Group.Leukemia,2012;26(7):1730-1741.
5 Wells DA,Benesch M,Loken MR,et al.Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation.Blood,2003;102(1):394-403.
6 Ogata K,Della Porta MG,Malcovati L,et al.Diagnostic utility of flow cytometry in low-grade myelodysplastic syndromes:a prospective validation study.Haematologica,2009;94(8):1066-1074.
7 Della Porta MG,Picone C,Pascutto C,et al.Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes:results of a European LeukemiaNET study.Haematologica,2012;97(8):1209-1217.
8 Bardet V,Wagner-Ballon O,Guy J,et al.Multicentric study underlining the interest of adding CD5,CD7 and CD56 expression assessment to the flow cytometric Ogata score in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.Haematologica,2015;100(4):472-478.
9 Cremers EMP,Westers TM,Alhan C,et al.Multiparameter flow cytometry is instrumental to distinguish myelodysplastic syndromes from non-neoplastic cytopenias.Eur J Cancer,2016;54:49-56.
10 Mathis S,Chapuis N,Debord C,et al.Flow cytometric detection of dyserythropoiesis:a sensitive and powerful diagnostic tool for myelodysplastic syndromes.Leukemia,2013;27(10):1981-1987.
11 Vardiman JW,Thiele J,Arber DA,et al.The 2008 revision of the World Health Organization(WHO)classification of myeloid neoplasms and acute leukemia:rationale and important changes.Blood,2009;114(5):937-951.
12 Cremers EM,Westers TM,Alhan C,et al.Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes.Haematologica,2017;102(2):320-326.
13 Lebrin F GM,Goumans MJ,Jonker L,et al.Endoglin promotes endothelial cell proliferation and TGF-b/ALK1 signal transduction.EMBO J,2004;23(20):4018-4028.
14 Gougos A St Jacgues S,Greaves A,et al.Identification of distinct epitopes of endoglin,an RGD-containing glycoprotein of endothelial cells,leukemic cells,and syncytiotrophoblasts.Int Immunol,1992;4(1):83-92.
15 Chen CZ,Li M,de Graaf D,et al.Identification of endoglin as a functional marker that defines long-term repopulating hematopoietic stem cells.Proc Natl Acad Sci U S A,2002;99(24):15468-15473.
16 Kapur NK,Morine KJ,Letarte M.Endoglin:a critical mediator of cardiovascular health.Vasc Health Risk Manag,2013;9:195-206.
17 Moody JL,Singbrant S,Karlsson G,et al.Endoglin is not critical for hematopoietic stem cell engraftment and reconstitution but regulates adult erythroid development.Stem Cells,2007;25(11):2809-2819.
18 Fajtova M,Kovarikova A,Svec P,et al.Immunophenotypic profile of nucleated erythroid progenitors during maturation in regenerating bone marrow.Leuk Lymphoma,2013;54(11):2523-2530.