Gu J, Zhang Q H, Huang Q H, Ren S X, Wu X Y, Ye M, Huang C H, Fu G, Zhou J, Niu C, Han Z G, Chen S J, Chen Z
Chinese National Human Genome Center at Shanghai, Shanghai 201203, PR China.
Hematol J. 2000;1(3):206-17. doi: 10.1038/sj.thj.6200020.
To address the molecular regulation of hematopoiesis and the complex mechanism in leukemogenesis, we established the first catalogs of genes expressed in normal bone marrow and leukemia CD34(+) cells.
CD34(+) cell cDNA libraries were constructed using mRNA from adult bone marrow and from a case of acute myeloid leukemia-M5 transformed from myelodysplastic syndrome (MDS-AML). Expressed sequence tags (ESTs) and full-length cDNAs were generated by sequencing and were annotated using bioinformatic tools.
From a total of 4142 ESTs obtained from normal bone marrow, 3424 meaningful tags were integrated into 1630 clusters, representing 622 known genes, 522 dbEST entries and 486 novel sequences. Out of 5382 ESTs from MDS-AML, 1985 clusters were produced based on the analysis of 4321 useful ESTs, including 711 known genes, 657 known ESTs and 617 novel sequences. Among 251 transcripts found in both bone marrow and MDS-AML EST datasets and those present in only one dataset, 58 showed statistically significant differences in EST copy numbers between the two tissues (P<0.05). Twenty putative full-length cDNAs for novel genes were also cloned from the MDS-AML library.
The distinct gene expression patterns in MDS-AML-CD34(+) cells as compared to normal control cells may contribute to the development and/or maintenance of the malignant phenotypes of leukemia cells.
为了研究造血作用的分子调控以及白血病发生的复杂机制,我们建立了首个正常骨髓和白血病CD34(+)细胞中表达基因的目录。
利用来自成人骨髓以及1例从骨髓增生异常综合征转化而来的急性髓系白血病-M5(MDS-AML)患者的mRNA构建CD34(+)细胞cDNA文库。通过测序产生表达序列标签(EST)和全长cDNA,并使用生物信息学工具进行注释。
从正常骨髓获得的总共4142个EST中,3424个有意义的标签被整合到1630个簇中,代表622个已知基因、522个dbEST条目和486个新序列。在来自MDS-AML的5382个EST中,基于对4321个有用EST的分析产生了1985个簇,包括711个已知基因、657个已知EST和617个新序列。在骨髓和MDS-AML EST数据集中均发现的251个转录本以及仅存在于一个数据集中的转录本中,有58个在两个组织之间的EST拷贝数上显示出统计学上的显著差异(P<0.05)。还从MDS-AML文库中克隆了20个新基因的推定全长cDNA。
与正常对照细胞相比,MDS-AML-CD34(+)细胞中独特的基因表达模式可能有助于白血病细胞恶性表型的发展和/或维持。