Pimenova M A, Parovichnikova E N, Kokhno A V, Domracheva E V, Manakova T E, Mal'tseva Iu S, Konnova M L, Shishigina L A, Savchenko V G
Ter Arkh. 2013;85(7):34-42.
To study and compare cytogenetic abnormalities in the bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic progenitor cells and in the BM mesenchymal stromal cells (MSCs) in patients with myelodysplastic syndrome (MDS). Subjects and methods. The results of a cytogenetic analysis of the total population of BM cells (BMC), CD34+ hematopoietic progenitor cells from BM and PB, and BM MSCs were analyzed in 35 patients (29 patients with MDS and 6 with MDS transformed into acute myeloid leukemia (AML)) and 7 healthy BM donors. Cytogenetic examinations were performed by G-banding of chromosomes and fluorescence in situ hybridization (FISH).
The BMC karyotype was abnormal in 17 (49%) of the 35 patients (13 with MDS and 4 with AML); the others were found to have a normal BM karyotype. The FISH analysis confirmed the same cytogenetic abnormalities in the BM and PB CD34+ hematopoietic progenitor cells in all the examinees with an abnormal karyotype. The mean abnormal clone sizes in the total population of BMCs and BM and PB CD34+ progenitor cells did not differ and constituted 65.8, 73.1, and 74.8%, respectively. The patients with a normal BM karyotype had no chromosome abnormalities in the CD34+ cells either. The karyotype of MSCs was analyzed in 23 (19 with MDS and 4 with AML) of the 35 patients. No karyotype abnormalities were revealed in the patients with MDS transformed into AML. There were structural chromosome aberrations in 2 (11%) of the 19 patients with MDS (one with constitutional inv(9)(p1 3q21) was found to have non-clonal translocation t(2;22)(p10;q1 1) and the other had a clone with an additional segment of the long arm of chromosome 2 in 35% of the cells. No numerical MSC karyotype abnormalities were detected. A normal MSC karyotype was defined in 7 healthy BM donors.
The cytogenetic analysis of hematopoietic and mesenchymal progenitor cells showed that the chromosome abnormalities revealed in these cell populations were different in the patients with MDS. The isolated CD34+ cells displayed the same cytogenetic abnormalities as in a total population of BMC. Examination of the latter could reveal no cytogenetic abnormalities in the majority of the patients. A normal BMC karyotype was detectable in the patients with AML. Two (11%) patients with MDS were found to have structural chromosome abnormalities that differed from those detected in the total population of BMC and in isolated CD34+ cells. The differences of chromosome abnormalities in the hematopoietic and mesenchymal progenitor cells point to the fact that the stromal microenvironment is not part of the abnormal clone in MDS, however, it may be of great importance in the pathogenesis of the disease.
研究并比较骨髓增生异常综合征（MDS）患者骨髓（BM）和外周血（PB）中CD34+造血祖细胞以及BM间充质基质细胞（MSC）的细胞遗传学异常情况。对象与方法。对35例患者（29例MDS患者和6例转化为急性髓系白血病（AML）的MDS患者）以及7名健康BM供者的BM细胞（BMC）总体、BM和PB中的CD34+造血祖细胞以及BM MSC进行了细胞遗传学分析。通过染色体G显带和荧光原位杂交（FISH）进行细胞遗传学检查。
35例患者中有17例（49%）（13例MDS患者和4例AML患者）的BMC核型异常；其余患者的BM核型正常。FISH分析证实，所有核型异常的受检者的BM和PB CD34+造血祖细胞存在相同的细胞遗传学异常。BMC总体、BM和PB CD34+祖细胞中异常克隆的平均大小无差异，分别为65.8%、73.1%和74.8%。BM核型正常的患者，其CD34+细胞也无染色体异常。对35例患者中的23例（19例MDS患者和4例AML患者）的MSC核型进行了分析。转化为AML的MDS患者未发现核型异常。19例MDS患者中有2例（11%）存在染色体结构畸变（1例具有先天性inv(9)(p13q21)的患者发现有非克隆性易位t(2;22)(p10;q11)，另1例患者35%的细胞中有一个带有2号染色体长臂额外片段的克隆）。未检测到MSC核型的数目异常。7名健康BM供者的MSC核型正常。
造血和间充质祖细胞的细胞遗传学分析表明，MDS患者这些细胞群体中所显示的染色体异常情况有所不同。分离出的CD34+细胞显示出与BMC总体相同的细胞遗传学异常。对BMC总体的检查在大多数患者中未发现细胞遗传学异常。AML患者可检测到正常的BMC核型。发现2例（11%）MDS患者存在与BMC总体和分离出的CD34+细胞中检测到的不同的染色体结构异常。造血和间充质祖细胞中染色体异常的差异表明，在MDS中基质微环境不是异常克隆的一部分，然而，它可能在疾病的发病机制中具有重要意义。
