骨髓增生异常综合征患者骨髓造血细胞分化抗原表达及其意义

Expression of differentiation antigens on bone marrow myeloid calls of the patients with myelodysplastic syndromes and it＇s clinical significances

目的了解骨髓增生异常综合征（MDS）患者骨髓成熟粒系和红系细胞分化抗原表达特点并分析其与IPSS、WPSS评分的相关性。方法采用流式细胞术检测34例（12例低危、22例高危）MDS患者及31名正常骨髓粒系CD11b、CD13、CD16、HLA-DR以及红系CD71和血型糖蛋白A（GlyA）抗原的序贯表达比例和模式。结果选择CD13／CD11b、CD13／CD16及CD11b／CD16组合来分析粒细胞分化抗原表达模式，对照组骨髓粒系细胞组合模式分别为“对钩”、“镰刀”或“反7”状，MDS患者骨髓粒系细胞发育分化中的抗原表达模式出现不同程度的改变。高危组CD11b-／CD11b＋比值（0．39±0．34）明显高于低危组（0．10±0．09）和对照组（0．07±0．05）（P〈0．01）；高危组CD16-／CD16＋比值（1．33±0．77）明显高于对照组（0．39±0．31）（P〈0．05）；低危和高危组骨髓粒细胞CD13的平均荧光强度（MFI）高于对照组，侧向角散射光信号（SSC）的MFI低于对照组，但差异无统计学意义。高危组CD11b—HIA—DR＋3．88％±3．07％、CD11b—HLA—DR-16．23％±15．59％、CD16-HLA—DR一41．12％±24．53％、CD11b＋CD16—33．53％±17．26％及CD13＋CD16—44．51％＋21．99％细胞占粒细胞比例明显高于低危组和对照组（P〈0．05），其他组间比较差异无统计学意义。应用CD71和GlyA的组合来分析红系细胞的分化，对照组两种抗原的组合模式均为双阳性表达，部分MDS患者可见CD71和G1yA表达不同步现象。低危组和高危组CD71＋和GlyA＋双阳性细胞分别占CD45-细胞和GlyA＋细胞的比例均显著低于对照组。MDS患者粒、红系抗原表达的比例和模式异常数目与IPSS积分（r=0．690，P=0．000）、WPSS积分（r=0．651，P=0．000）均呈正相关。结论MDS患者造血细胞分化抗原表达异常，异常程度与预后相关。这提示分化抗原检测可能有助于MDS患者的诊断和预后判断。

Objective To detect the abnormal differentiation of bone marrow myeloid cells in myelodysplastie syndromes （MDS） and its correlation with the prognosis of MDS patients. Methods Quantitative assessment of CD11 b, CD13, CD16 and HLA-DR expression on the membrane of bone marrow granulocytes, and CD71 and glyeopborin A on erythroblasts of 12 MDS patients in low-risk, 22 in high-risk and 31 normal controls was conducted with flow cytometry. The correlation between the abnormality and the prognosis of MDS cases were analyzed. Results The granulocytic differentiation was analyzed with the combinations of CD13/CD11 b, CD13/CD16 and CD11b/CD16. The ＂right hook＂, ＂sickle＂ and ＂retroflex 7＂ shape expressions were found in normal controls while there were various changes in MDS groups. The ratios of CD11b -/CD11b ＋ （0. 39 ±0. 34）and CD16 -/CD16 ＋ （1.33 ±0. 77） were significantly higher in high-risk MDS group than those of control group （0. 07 ±0. 05 and 0. 39±0. 31 respectively） （P 〈0. 05）.The MFI （ mean fluorescence index） of SSC （ side scatter） in the granulocyte gate of MDS groups was lower while MFI of CD13 was higher. The mean percentages of CDllb- HLA- DR ＋ 3.88% ＋ 3.07%, CDllb- HLA - DR - 16. 23% ＋ 15.59%, CD16 - HLA - DR - 41.12% -＋24.53%, CDllb ＋ CD16 - 33.53% ± 17.26% and CD13 ＋ CD16 - 44. 51% ± 21.99% granulocytes of high-risk MDS group were significantly higher than those of low-risk and control groups （P 〈 0. 05 ）. The erythroid cell lineage differentiation was analyzed with CD71/glycophorin A combination. Double positive expression was found in all controls, but asynchronous expression of CD71/glycophorin A was found in some MDS cases. The mean percentage of double positive cells in CD45 - and glycophorin A ＋ cell population was significantly lower in low-risk and high-risk MDS groups. The abnormal numbers and patterns of the antigen expression of MDS cases per case correlated directly with their IPSS （ international prognostic scoring system） （ r = 0. 690, P = 0. 000） and WPSS （WHO adapted prognostic scoring system） （r = 0. 651, P = 0. 000） scores. Conclusion There is an abnormal expression of differentiation antigens on bone marrow myeloied cells of MDS patients. And the severity is correlated with the prognosis. The abnormal differentiation of myeloid cells is probably involved in the pathogenesis of MDS. So the examination of these antigenic expressions with flow cytometry might be helpful for diagnosis and prognosis of MDS.