骨髓增生异常综合征克隆细胞生物学特征的初步研究

Preliminary study of biological charateristics of myelodysplastic syndromes clonal cells

目的研究骨髓增生异常综合征(MDS)克隆细胞和急性髓系白血病(AML)克隆细胞的部分生物学差异。方法对经核型分析证实有克隆标志的51例 MDS 和11例 AML 患者骨髓中克隆细胞(荧光原位杂交分析)和原始细胞百分比进行比较;检测 MDS 患者骨髓中晚期红系(血型糖蛋白A阳性的晚幼红细胞)、粒系(DAPI 复染可分辨的分叶核细胞)和巨核系(CD61阳性磁珠分选,CD41阳性的形态学成熟的巨核细胞)中克隆细胞比例;同步检测 MDS 患者骨髓及外周血中克隆细胞比例;用流式细胞术检测含有克隆细胞的 MDS 患者外周血中性粒细胞的吞噬和氧化功能并与正常人和AML 患者标本比较。结果 MDS 患者骨髓克隆细胞百分比(平均48.2%)均高于原始细胞(平均6.7%)(P<0.01)。进展型 MDS 与非进展型相比,克隆细胞与原始细胞数更接近。单纯染色体+8异常与单纯5q-患者比较,克隆细胞与原始细胞数量更接近。而在11例 AML 患者,克隆细胞与原始细胞百分比的平均差距接近零。在 MDS 患者骨髓细胞中检出相当数量带有克隆标志的晚期造血细胞:分叶核细胞中平均为45.9%;晚幼红细胞中为46.0%;成熟巨核细胞中为38.0%。MDS 患者外周血中检出与骨髓中核型一致的克隆细胞,数量与骨髓中克隆细胞数相关(骨髓中平均为48.6%,外周血中为37.3%)。功能性检测显示 MDS 患者外周血中的中性粒细胞具有与正常对照者几乎一致的对DHR 的摄取和氧化功能(P>0.05)。结论 MDS 克隆细胞与 AML 克隆细胞具有明显的生物学差异。

Objective To investigate the biological difference of clonal cells between myelodysplastic syndromes（MDS） and acute myeloid leukemia（AML）. Method Bone marrow（BM） clonal cells （which had cytogenetic markers detected by FISH assay） and blasts were quantitively analysed in 51 MDS and 11 AML patients. The clonal cell percentage in orthochromatic normoblasts, granulocytes and megakaryocytes were assayed. The biological functions for phagocytosis and oxidation of MDS peripheral blood（PB） neutrophils were compared with that of normal controls. Results Almost all MDS patients BM had a higher clonal cell percentage（ mean 48.2% ） than blasts percentage（ mean 6.7% ） （ P 〈 0. 01 ）, but with the subtype of MDS advancing this percentage gap was closing up, and in 11 AML patients no such gap was observed. This gap in MDS patients with ＋ 8 abnormality was smaller than in those with 5q - In MDS BM, clonal cells were detected in segmented granulocytes （ mean 45.9% ）, orthochromatic normoblasts （ mean 46.0% ） and mature megakaryocytes （ mean 38.0% ）. In Addition, an approximate amount of clonal cells with the same karyotype abnormality in BM were detected in MDS PB （mean 37.3% in blood vs 48.6% in marrow）. Functional analysis showed that the neutrophils in MDS PB could exert nearly normal physiological functions （ P 〉 0.05 ）, but those from AML could not as compared to healthy donors （ P 〈 0.01 ）. Conclusion There is a significant difference in the biological features between MDS and AML clonal cells.