难治性急性髓系白血病(M_(2a))的基因表达谱

Gene Expression Profile of Refractory Acute Myeloid Leukemia (M_(2a))

背景与目的:复发是急性髓系白血病(acutemyeloidleukemia,AML)治疗失败的主要原因,部分AML复发时其免疫表型和细胞遗传学已发生了改变。耐药是AML难治的主要原因,AML耐药与基因的异常表达有关,目前对AML复发/难治或耐药相关基因及其表达所知甚少。本研究检测AML初诊与复发/难治之间的基因表达差异,为阐明AML复发/难治的可能机制提供依据。方法:应用基因芯片技术,对5例自身配对初诊与复发/难治AML鄄M2a患者之间骨髓单个核细胞的基因表达差异进行了检测。结果:在检测的925个基因中,14个基因在初诊与复发/难治AML鄄M2a之间差异表达,其中12个基因(涉及细胞信号转导、DNA复制、转录调节和RNA加工以及细胞循环等相关基因)在复发时明显上调,参与DNA复制过程的RRM1基因上调最显著。结论:在AML鄄M2a复发/难治的发生过程中有多个基因共同参与,这些基因的高表达提示复发/难治AML细胞增殖能力可能更强。

BACKGROUND & OBJECTIVE:Recurrence is the major cause of treatment failure of acute myeloid leukemia (AML). At recurrence, some patients show changes in immunophenotype and cytogenetics. Drug resistance, the main cause of refractoriness of AML, is related to abnormal genes expression. This study was to detect differential expression of genes in naive and recurrent/refractory AML, and explore potential mechanisms of recurrent/refractory AML. METHODS: Differential gene expressions of bone marrow mononuclear cells between naive and recurrent/refractory diseases in 5 self-paired patients with AML-M2a were detected by DNA microarray. RESULTS: In 925 tested genes, 14 were differentially expressed between naive and recurrent/refractory diseases in the 5 self-paired patients. Of the 14 genes, 12 (involved in signal transduction, DNA replication, regulation of transcription, RNA processing, and regulation of cell cycle) were obviously up-regulated in recurrent diseases, and up-regulation of RRM1 (involved in DNA replication) was the most obvious. CONCLUSIONS: Development of recurrent/refractory AML-M2a is concerned with various genes. Up-regulation of these genes suggests that proliferation of recurrent/refractory AML-M2a blasts may be higher than that of naive AML-M2a blasts.