骨髓增生异常综合征难治性贫血伴原始细胞增多Ⅱ型的免疫学特征和预后相关研究(英文)

Immunologic Characteristics and Prognosis of Myelodysplastic Syndrome New Subtype:Refractory Anemia with Excess Blasts-Ⅱ

本研究探讨骨髓增生异常综合征(MDS)中WHO亚型难治性贫血伴原始细胞增多II型(RAEB-II)的免疫学特征,并筛选出与MDS预后相关的免疫学指标。采用CD45/SSC双参数散点设门,应用三色流式细胞术对35例原发MDS患者骨髓标本进行流式细胞术检测,并对其进行随访。另外,选择同时期47例AML-M1、51例AML-M2及38例ALL初诊患者作为对照。对免疫分型结果结合随访应用SPSS13.0软件包进行数据处理。结果显示:RAEB-II患者高表达HLA-DR(100%),有较高的灵敏度及特异性。在RAEB-II中表达相对较高的还有CD13(94.74%)、CD33(84.21%)和CD117(78.95%)。与MDS其它亚型相比,CD13在REAB-II中的表达高于RCMD(p<0.01)及REAB-I(p<0.05);CD33、CD117(p<0.05)及干细胞抗原CD34(p<0.01)在RAEB-II中的表达高于RC-MD,但与RAEB-I的表达没有显著性差异(p>0.05)。与AML-M1和AML-M2相比,RAEB-II中CD13和CD117的表达无显著差别(p>0.05);CD33(p<0.01)和CD34(p<0.05)表达均低于AML-M1,而与AML-M2表达无显著差别(p>0.05);CD15(p<0.01)和CD11b(p<0.05)表达低于AML-M2,而与AML-M1相比表达无显著差别(p>0.05);RAEB-II中MPO的表达低于AML-M1和AML-M2(p<0.05);HLA-DR表达高于AML-M2(p<0.05),与AML-M1表达无显著差别(p>0.05)。与T-ALL相比,RAEB-II不表达CD2、CD3、CD5和CD8(阳性率为0%,p<0.01);CD4(p<0.05)和CD7(p<0.01)表达均低于T-ALL。与B-ALL相比,CD19和CD20在RAEB-II中不表达(阳性率为0%,p<0.01);CD10、CD22和cCD79a表达均低于T-ALL(p<0.05)。CD117(p=0.0197)及MPO(p=0.0085)是影响本组MDS总存活期(OS)的主要免疫学标志;Cox回归显示CD117(p=0.003)为OS最主要影响因素。结论:RAEB-II以髓系抗原表达为主,基本不表达或者低表达淋巴系抗原,似乎有着自己较独特的免疫表型特征。HLA-DR可作为RAEB-II的特异性指标与MDS其它亚型相鉴别。CD117有望成为判断MDS预后的独立指标。

This study was aimed to investigate the immunologic characteristics of refractory anemia with excess blasts-Ⅱ （RAEB-Ⅱ） which belongs to a new subtype of World Health Organization （WHO） classification of myelodysplastic syndrome （MDS） and to screen out the independent immunologic prognostic factors of MDS. 35 cases of adult patients with de novo MDS were investigated. The imrnunofluorescent analysis by multiparameter flow cytometry was performed at the double gating of CD45/SSC to determine the immunophenotype of MDS cells in all cases. All patients were followed up. 47 cases of acute myeloid leukemia （AML） M1,51 cases of AML-M2 and 38 cases of acute lymphocytic leukemia （ALL） were selected as control. Software SPSS 13.0 was applied to analyze all the related data. The results showed that the positive expression rate of HLA-DR in RAEB-Ⅱ was 100%, which was high in sensitivity and specificity. CD13 （94.74%）, CD33（84.21% ） and CD117（78.95% ） were also highly expressed in RAEB-Ⅱ. CD13 in RAEB-Ⅱ was significantly higher than that in refractory cytopenia with or without multilineage dysplasia （RA/RCMD） （p 〈0.01）and REAB-Ⅰ（p 〈0.05） ; CD33,CDl17（p 〈0.05）and stem cell antigen CD34（p 〈0.01）in RAEB-Ⅱ were significantly higher than that in RCMD（p 〈0.01 ）, but no statistically significant difference was found as compared with RAEB-Ⅰ （p 〉 0.05 ）. Compared with AML-M1 and AML-M2, no significant difference of CD13 and CD117 in RAEB-Ⅱ was found （p 〉 0.05 ）. CD33 （p 〈 0.01 ） and CD34 （p 〈 0.05 ） were significantly lower than that in AML-M1, but no significant difference was found as compared with AML-M2 （p 〉 0.05 ） ; CD15 （p 〈 0.01 ） and CD11b （p 〈 0.05 ） was significantly lower than that in ME, but no significant difference was found as compared with AML-M1 （ p 〉 0.05 ） ; MPO was significantly lower than that in AML-M1 and M2 （p 〈0. 05） ; HLA-DR was significantly higher than that on AML-M2 （p 〈 0.05 ）, but no significant difference was found as compared with AML-M1 （p 〉 0.05 ）. RAEB-Ⅱ did not express CD2, CD3, CD5 and CD8 （ positive rate 0%, p 〈 0.01 ） when compared with T-ALL; CD4 （p 〈 0.05 ） and CD7（p 〈0.01 ） were significantly lower than that in T-ALL. RAEB-Ⅱ did not express CD19 and CD20 （positive rate 0%, p 〈0.01 ） as compared with B-ALL; CD10, CD22 and cCD79a were significantly lower than that in B-ALL（p 〈 0.05 ）. CD117 （p = 0. 0197 ） and MPO（p = 0. 0085 ） were the two prognostic immunological antigens as regards the overall survival （OS） of MDS; CD117 （p = 0.003 ）was the single parameter in Cox regression. It is concluded that RAEB-Ⅱ expresses mainly myeloid antigen without or with little expression of lymphoid antigen. Unique individual immunophenotypic features can be detected in patients with RAEB-Ⅱ. HLA-DR can be a specific parameter to distinguish the other subtypes of MDS. CD117 may be an independent prognostic immunological antigen as regards OS of MDS.