Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
Mol Cancer. 2010 Feb 22;9:41. doi: 10.1186/1476-4598-9-41.
Expression levels of the cell surface glycoprotein, CD7, and the serine protease, elastase 2 (ELA2), in the leukemic cells of patients with chronic myeloid leukemia (CML) have been associated with clinical outcome. However, little is known about the mechanisms that underlie the variable expression of these genes in the leukemic cells.
To address this question, we compared the level of their expression with the DNA methylation and histone acetylation status of 5' sequences of both genes in leukemic cell lines and primitive (lin-CD34+) leukemic cells from chronic phase CML patients. DNA methylation of the ELA2 gene promoter did not correlate with its expression pattern in lin-CD34+ cells from chronic phase CML patient samples even though there was clear differential DNA methylation of this locus in ELA2-expressing and non-expressing cell lines. In contrast, we found a strong relation between CD7 expression and transcription-permissive chromatin modifications, both at the level of DNA methylation and histone acetylation with evidence of hypomethylation of the CD7 promoter region in the lin-CD34+ cells from CML patients with high CD7 expression.
These findings indicate a link between epigenetic modifications and CD7 expression in primitive CML cells.
慢性髓性白血病（CML）患者白血病细胞表面糖蛋白 CD7 和丝氨酸蛋白酶 2（ELA2）的表达水平与临床结果相关。然而，对于这些基因在白血病细胞中表达的可变机制知之甚少。
为了解决这个问题，我们比较了白血病细胞系和慢性期 CML 患者原始（lin-CD34+）白血病细胞中这两个基因 5'序列的表达水平与 DNA 甲基化和组蛋白乙酰化状态。尽管在表达和不表达 ELA2 的细胞系中，ELA2 基因启动子的 DNA 甲基化存在明显差异，但它与慢性期 CML 患者样本中 lin-CD34+细胞的表达模式没有相关性。相比之下，我们发现 CD7 表达与转录允许染色质修饰之间存在很强的关系，无论是在 DNA 甲基化还是组蛋白乙酰化水平上，都有证据表明在高 CD7 表达的 CML 患者的 lin-CD34+细胞中 CD7 启动子区域的低甲基化。
这些发现表明在原始 CML 细胞中，表观遗传修饰与 CD7 表达之间存在联系。
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