He Qi, Chang Chun-Kang, Xu Feng, Zhang Qing-Xia, Shi Wen-Hui, Li Xiao
The Hematology Department of the Sixth Hospital affiliated with Shanghai Jiaotong University, Shanghai, China, 200233.
PLoS One. 2015 Oct 15;10(10):e0140372. doi: 10.1371/journal.pone.0140372. eCollection 2015.
Malignant clonal cells purification can greatly benefit basic and clinical studies in myelodysplastic syndrome (MDS). In this study, we investigated the potential of using type 1 insulin-like growth factor receptor (IGF-IR) as a marker for purification of malignant bone marrow clonal cells from patients with MDS. The average percentage of IGF-IR expression in CD34+ bone marrow cells among 15 normal controls was 4.5%, 70% of which also express the erythroid lineage marker CD235a. This indicates that IGF-IR mainly express in erythropoiesis. The expression of IGF-IR in CD34+ cells of 55 MDS patients was significantly higher than that of cells from the normal controls (54.0 vs. 4.5%). Based on the pattern of IGF-IR expression in MDS patients and normal controls, sorting of IGF-IR-positive and removal of CD235a-positive erythroid lineage cells with combination of FISH detection were performed on MDS samples with chromosomal abnormalities. The percentage of malignant clonal cells significantly increased after sorting. The enrichment effect was more significant in clonal cells with a previous percentage lower than 50%. This enrichment effect was present in samples from patients with +8, 5q-/-5, 20q-/-20 or 7q-/-7 chromosomal abnormalities. These data suggest that IGF-IR can be used as a marker for MDS bone marrow clonal cells and using flow cytometry for positive IGF-IR sorting may effectively purify MDS clonal cells.
恶性克隆细胞的纯化对骨髓增生异常综合征（MDS）的基础和临床研究大有裨益。在本研究中，我们探究了使用1型胰岛素样生长因子受体（IGF-IR）作为从MDS患者中纯化恶性骨髓克隆细胞的标志物的潜力。15名正常对照者CD34+骨髓细胞中IGF-IR表达的平均百分比为4.5%，其中70%也表达红系标志物CD235a。这表明IGF-IR主要在红细胞生成中表达。55例MDS患者CD34+细胞中IGF-IR的表达显著高于正常对照者的细胞（54.0%对4.5%）。基于MDS患者和正常对照者中IGF-IR的表达模式，对伴有染色体异常的MDS样本进行IGF-IR阳性分选并去除CD235a阳性红系细胞，并结合荧光原位杂交（FISH）检测。分选后恶性克隆细胞的百分比显著增加。在先前百分比低于50%的克隆细胞中，富集效果更为显著。这种富集效果在伴有+8、5q-/-5、20q-/-20或7q-/-7染色体异常的患者样本中均存在。这些数据表明IGF-IR可作为MDS骨髓克隆细胞的标志物，利用流式细胞术进行IGF-IR阳性分选可有效纯化MDS克隆细胞。
