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通过膜联蛋白V流式细胞术检测凋亡指数:作为骨髓增生异常综合征形态学和细胞遗传学诊断的辅助手段

Apoptotic index by Annexin V flow cytometry: adjunct to morphologic and cytogenetic diagnosis of myelodysplastic syndromes.

作者信息

Merchant S H, Gonchoroff N J, Hutchison R E

机构信息

Department of Pathology, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA.

出版信息

Cytometry. 2001 Feb 15;46(1):28-32. doi: 10.1002/1097-0320(20010215)46:1<28::aid-cyto1034>3.0.co;2-h.

DOI:10.1002/1097-0320(20010215)46:1<28::aid-cyto1034>3.0.co;2-h
PMID:11241504
Abstract

The myelodysplastic syndromes (MDS) are clonal hematologic malignancies characterized by pancytopenia, dysplastic hematopoiesis, and a propensity to leukemic transformation. Increased apoptosis has been noted in MDS as a possible explanation for ineffective hematopoiesis, with lower levels in progression to and in de novo acute leukemia. Apoptosis can be measured by binding of Annexin V to exposed membrane phosphatidylserine. We postulated that the apoptotic index would aid in the differential diagnosis of MDS versus other hematopoietic diseases. We examined 33 bone marrow aspirates suspected of hematopoietic malignancy for apoptotic index by Annexin V analysis using a Becton Dickinson FACStar+ flow cytometer. The apoptotic index was expressed as the percentage of Annexin V-positive cells divided by total mononuclear cells in the gate. By standard morphologic analysis, 16 cases were diagnosed as MDS (9 refractory anemia [RA], 2 refractory anemia with ringed sideroblasts [RARS], 1 refractory anemia with excess of blasts [RAEB], 3 chronic myelomonocytic leukemia [CMML], and 1 unclassified), 11 as acute leukemia (AL), 6 as myeloproliferative disorders (MPD). Eight cases (uninvolved marrow of five patients with lymphoproliferative disorders [LPD], one patient with multiple myeloma, and two patients with anemia of chronic disease) served as nonneoplastic controls. A higher degree of apoptosis was observed in MDS (mean = 44.7%; range = 29.5--60%) compared with MPD (mean = 8.2%; range = 2.3--15.4%), AL (mean = 16.1%; range = 5.1--29.4%), and control marrow samples (mean = 11.6%; range = 1.5--21%). Additionally, the apoptotic index was significantly higher in MDS compared with MPD (P < 0.0001). In conclusion, a high apoptotic index occurs in MDS, supporting previous reports and suggesting that Annexin V analysis can be used as an adjunct in the diagnosis of MDS versus MPD. This would be particularly useful for the often-difficult distinction between early MDS and early MPD cases with equivocal morphology.

摘要

骨髓增生异常综合征(MDS)是一类克隆性血液系统恶性肿瘤,其特征为全血细胞减少、造血发育异常以及有白血病转化倾向。MDS中已观察到凋亡增加,这可能是无效造血的一种解释,而在进展为新发急性白血病时凋亡水平较低。凋亡可通过膜联蛋白V与暴露的膜磷脂酰丝氨酸结合来检测。我们推测凋亡指数有助于MDS与其他造血系统疾病的鉴别诊断。我们使用Becton Dickinson FACStar +流式细胞仪通过膜联蛋白V分析检测了33份疑似造血系统恶性肿瘤的骨髓穿刺液的凋亡指数。凋亡指数表示为膜联蛋白V阳性细胞占门内总单核细胞的百分比。通过标准形态学分析,16例被诊断为MDS(9例难治性贫血[RA],2例环形铁粒幼细胞性难治性贫血[RARS],1例原始细胞过多的难治性贫血[RAEB],3例慢性粒单核细胞白血病[CMML],1例未分类),11例为急性白血病(AL),6例为骨髓增殖性疾病(MPD)。8例(5例淋巴增殖性疾病[LPD]患者的未受累骨髓、1例多发性骨髓瘤患者和2例慢性病贫血患者)作为非肿瘤对照。与MPD(平均= 8.2%;范围= 2.3-15.4%)、AL(平均= 16.1%;范围= 5.1-29.4%)和对照骨髓样本(平均= 11.6%;范围= 1.5-21%)相比,MDS中观察到更高程度的凋亡。此外,MDS的凋亡指数显著高于MPD(P <0.0001)。总之,MDS中出现高凋亡指数,支持先前的报道,并表明膜联蛋白V分析可作为MDS与MPD诊断的辅助手段。这对于早期MDS与形态学不明确的早期MPD病例之间常常困难的区分将特别有用。

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