巨核细胞生成
血小板生成素
生物
膜联蛋白
基因表达谱
巨核细胞
细胞凋亡
分子生物学
基因表达
骨髓
基因
癌症研究
造血
川地34
融合基因
微阵列分析技术
膜联蛋白A5
细胞生物学
免疫学
干细胞
遗传学
作者
Elena Tenedini,Maria Elena Fagioli,Nicola Vianelli,Pier Luigi Tazzari,Francesca Ricci,Enrico Tagliafico,Paolo F. Ricci,Luigi Gugliotta,Giovanni Martinelli,S Tura,Michele Baccarani,Sérgio Ferrari,Lucia Catani
出处
期刊:Blood
[American Society of Hematology]
日期:2004-11-15
卷期号:104 (10): 3126-3135
被引量:70
标识
DOI:10.1182/blood-2003-07-2597
摘要
Abstract Gene expression profiles of bone marrow (BM) CD34-derived megakaryocytic cells (MKs) were compared in patients with essential thrombocythemia (ET) and healthy subjects using oligonucleotide microarray analysis to identify differentially expressed genes and disease-specific transcripts. We found that proapoptotic genes such as BAX, BNIP3, and BNIP3L were down-regulated in ET MKs together with genes that are components of the mitochondrial permeability transition pore complex, a system with a pivotal role in apoptosis. Conversely, antiapoptotic genes such as IGF1-R and CFLAR were up-regulated in the malignant cells, as was the SDF1 gene, which favors cell survival. On the basis of the array results, we characterized apoptosis of normal and ET MKs by time-course evaluation of annexin-V and sub-G1 peak DNA stainings of immature and mature MKs after culture in serum-free medium with an optimal thrombopoietin concentration, and annexin-V–positive MKs only, with decreasing thrombopoietin concentrations. ET MKs were more resistant to apoptosis than their normal counterparts. We conclude that imbalance between proliferation and apoptosis seems to be an important step in malignant ET megakaryocytopoiesis.
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