Blau Olga, Hofmann Wolf-Karsten, Baldus Claudia Dorothea, Thiel Gundula, Serbent Verena, Schümann Elke, Thiel Eckhard, Blau Igor Wolfgang
Department of Hematology, Oncology and Transfusion Medicine, Charité-Campus Benjamin Franklin, University School of Medicine, Berlin, Germany.
Exp Hematol. 2007 Feb;35(2):221-9. doi: 10.1016/j.exphem.2006.10.012.
Bone marrow mesenchymal stroma cells (BMSC) are key components of the hematopoietic microenvironment. The question of whether BMSC from patients with hematological disorders have cytogenetic abnormalities is discussed controversially, some studies indicating that they are cytogenetically normal and others providing evidence of their aberrations.
We performed standard and molecular cytogenetic analyses of both hematopoietic cells and BMSC from 31 patients with myelodysplastic syndrome (MDS, n = 18) and acute myeloid leukemia (AML, n = 13) and 7 healthy individuals. Mononuclear cells were isolated from fresh bone marrow aspirates at the time of initial diagnosis for cytogenetic analysis of hematopoietic cells (HC) and selection of BMSC.
Clonal cytogenetic aberrations were observed in HC from 8 (44%) MDS and 8 (61%) AML patients. Cytogenetic analyses of BMSC were successfully performed in 27 of the 31 cases. Structural chromosomal aberrations, including t(1;7), t(4;7), t(7;9), t(7;10), t(7;19), t(15;17), and others, were detectable in BMSC from 7 of 16 (44%) MDS and 6 of 11 (54%) AML patients. The breakpoints of chromosomes in BMSC were typical for leukemia aberrations. Two patients showed clonal chromosomal markers.
BMSC from MDS and AML patients show chromosomal abnormalities. Although the majority of cytogenetic aberrations in BMSC were not clonal and differed from chromosomal markers in HC from the same individual, detection of typical chromosomal changes in BMSC suggests enhanced genetic susceptibility of these cells in MDS/AML. This may indicate potential involvement of BMSC in the pathophysiology of MDS/AML.
骨髓间充质基质细胞（BMSC）是造血微环境的关键组成部分。血液系统疾病患者的BMSC是否存在细胞遗传学异常这一问题存在争议，一些研究表明它们细胞遗传学正常，而另一些研究则提供了其存在畸变的证据。
我们对31例骨髓增生异常综合征（MDS，n = 18）和急性髓系白血病（AML，n = 13）患者以及7名健康个体的造血细胞和BMSC进行了标准和分子细胞遗传学分析。在初次诊断时从新鲜骨髓穿刺物中分离单核细胞，用于造血细胞（HC）的细胞遗传学分析和BMSC的选择。
在8例（44%）MDS和8例（61%）AML患者的HC中观察到克隆性细胞遗传学畸变。31例中有27例成功进行了BMSC的细胞遗传学分析。在16例MDS患者中的7例（44%）和11例AML患者中的6例（54%）的BMSC中可检测到结构染色体畸变，包括t(1;7)、t(4;7)、t(7;9)、t(7;10)、t(7;19)、t(15;17)等。BMSC中染色体的断点是白血病畸变的典型特征。两名患者显示出克隆性染色体标记。
MDS和AML患者的BMSC显示出染色体异常。尽管BMSC中的大多数细胞遗传学畸变不是克隆性的，且与同一个体HC中的染色体标记不同，但在BMSC中检测到典型的染色体变化表明这些细胞在MDS/AML中遗传易感性增强。这可能表明BMSC参与了MDS/AML的病理生理学过程。
