Institute of Biomedicine of Salamanca, Institute of Molecular and Cellular Biology of Cancer, Center of Cancer Research, University of Salamanca-CSIC, Spain.
Pharmacogenet Genomics. 2012 May;22(5):381-8. doi: 10.1097/FPC.0b013e328351f3e9.
Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. It is well known that CML cells are genetically unstable. However, the mechanisms by which these cells acquire genetic alterations are poorly understood. Imatinib mesylate is the standard therapy for newly diagnosed CML patients. Imatinib mesylate targets the oncogenic kinase activity of BCR-ABL.
To study the gene expression profile of bone marrow hematopoietic cells in the same patients with CML before and 1 month after imatinib therapy.
Samples from patients with CML were analyzed using Affymetrix GeneChip Expression Arrays.
A total of 594 differentially expressed genes, most of which (393 genes) were downregulated, as a result of imatinib therapy were observed.
The blockade of oncoprotein Bcr-Abl by imatinib could cause a decrease in the expression of key DNA repair genes and substantially modify the expression profile of the bone marrow cells in the first days of therapy.
慢性髓性白血病（CML）是一种造血系统的恶性克隆性疾病，由 BCR/ABL 融合癌基因的表达引起。众所周知，CML 细胞的遗传不稳定。然而，这些细胞获得遗传改变的机制还知之甚少。甲磺酸伊马替尼是新诊断的 CML 患者的标准治疗方法。甲磺酸伊马替尼针对 BCR-ABL 的致癌激酶活性。
研究 CML 患者在伊马替尼治疗前和治疗后 1 个月骨髓造血细胞的基因表达谱。
使用 Affymetrix GeneChip Expression Arrays 分析 CML 患者的样本。
共观察到 594 个差异表达基因，其中大多数（393 个）基因由于伊马替尼治疗而下调。
伊马替尼对癌蛋白 Bcr-Abl 的阻断可能导致关键 DNA 修复基因的表达降低，并在治疗的最初几天内显著改变骨髓细胞的表达谱。
