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骨髓增生异常综合征CD34+细胞的增殖与分化:骨髓CD34+细胞的表型亚群

Proliferation and differentiation of myelodysplastic CD34+ cells: phenotypic subpopulations of marrow CD34+ cells.

作者信息

Sawada K, Sato N, Notoya A, Tarumi T, Hirayama S, Takano H, Koizumi K, Yasukouchi T, Yamaguchi M, Koike T

机构信息

Department of Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.

出版信息

Blood. 1995 Jan 1;85(1):194-202.

PMID:7528567
Abstract

In a search for a mechanism to explain the impaired growth of progenitor cells in patients with myelodysplastic syndromes (MDS), marrow CD34+ cells were purified up to 94.9% +/- 4.2% for normal individuals and 88.1% +/- 17.6% for MDS patients, using monoclonal antibodies and immunomagnetic microspheres (MDS CD34+ cells). Phenotypic subpopulations of these CD34+ cells were analyzed for CD38, HLA-DR, CD33, CD13, CD14, CD41 and CD3 plus CD19, in association with proliferative and differentiative capacities. The 15 studies performed included 12 MDS patients. Coexpression rate of CD13 significantly increased in the MDS CD34+ cell population with a value of 91.4% +/- 11.6% and ranging from 60.3% to 100%, and exceeded 99% in four studies, whereas that of normal CD34+ cells was 49.9% +/- 15.8%, ranging from 28.2% to 70.1% (P < .001). Coexpression rate of CD38, HLA-DR, CD33, CD14, and CD3 plus CD19 in MDS CD34+ cells did not significantly differ from that of normal CD34+ cells. The total number of colonies and clusters grown from 100 normal marrow CD34+ cells was 40.4 +/- 8.6, the range being from 27.2 to 50.3; this varied in MDS marrow CD34+ cells with a value of 34.0 +/- 28.7, the range being 0 to 95.9. The lineage of colonies and clusters promoted by MDS marrow CD34+ cells was predominantly committed to nonerythroid with impaired differentiation in 13 of 15 studies (87%). CD13 is first expressed during hematopoiesis by colony-forming unit granulocyte-macrophage and is absent in erythroid progenitors. Therefore, this study provides direct evidence for the lineage commitment of MDS CD34+ cells to nonerythroid with impaired differentiation and explains the mechanism of nil or low colony expression of MDS progenitor cells to erythroid lineage.

摘要

为探寻一种机制来解释骨髓增生异常综合征(MDS)患者祖细胞生长受损的原因,利用单克隆抗体和免疫磁珠对正常个体的骨髓CD34⁺细胞进行纯化,纯度高达94.9%±4.2%,对MDS患者的骨髓CD34⁺细胞(MDS CD34⁺细胞)纯化后的纯度为88.1%±17.6%。分析这些CD34⁺细胞的表型亚群的CD38、HLA-DR、CD33、CD13、CD14、CD41以及CD3加CD19,并结合其增殖和分化能力进行研究。所进行的15项研究纳入了12例MDS患者。MDS CD34⁺细胞群体中CD13的共表达率显著升高,为91.4%±11.6%,范围在60.3%至100%之间,在4项研究中超过99%,而正常CD34⁺细胞的共表达率为49.9%±15.8%,范围在28.2%至70.1%之间(P<0.001)。MDS CD34⁺细胞中CD38、HLA-DR、CD33、CD14以及CD3加CD19的共表达率与正常CD34⁺细胞相比无显著差异。100个正常骨髓CD34⁺细胞生长的集落和簇的总数为40.4±8.6,范围在27.2至50.3之间;MDS骨髓CD34⁺细胞的这一数值有所不同,为34.0±28.7,范围在0至95.9之间。在15项研究中的13项(87%)中,MDS骨髓CD34⁺细胞促进形成的集落和簇的谱系主要倾向于非红系,且分化受损。CD13在造血过程中首先由粒-巨噬细胞集落形成单位表达,而红系祖细胞中不存在。因此,本研究为MDS CD34⁺细胞向非红系谱系分化且分化受损提供了直接证据,并解释了MDS祖细胞对红系谱系集落表达为零或低的机制。

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