急性白血病患者基因表达谱变化的初步研究

A pilot study of spectrum of gene expression of acute leukemia

目的 研究急性白血病发病机理,寻找诊断分型、预后判断及治疗等方面的新方法。方法 采用基因芯片技术观察了22例初发急性白血病患者12848条基因的表达谱,分析基因表达特征。结果 12848条基因中有1163条基因差异表达,其中45条基因与Golub等报道的50条急性淋巴细胞白血病(ALL)、急性髓性白血病(AML)的预测基因一致,并符合ALL、AML的分型标准;在耐药细胞系K562 n/VCR中高表达的7条基因在6例难治性急性白血病患者中也过度表达;进一步分析AML各亚型及ALL的表达谱差异,发现31条基因在AMLM1 M3亚型中的表达与AMLM4 M6亚型及ALL明显不同。结论 支持Golub等提出的急性白血病分型标准,临床上成人ALL和AMLM4 M6亚型的预后较AMLM1 M3亚型差,与一系列基因表达的改变有关。原发耐药可能是导致白血病难治的主要原因之一。基因芯片对于急性白血病分型诊断及预后判断具有重要意义。

Objective To investigate the gene expression of acute leukemia so as to study the pathogenesis of leukemia. Methods Five ml of bone marrow was collected from 22 patients with leukemia, 15 males and 7 females, aged 15-86, 17 with acute myelocytic leukemia, 4 with acute lymphocytic leukemia, and 1 with AHL. Mononuclear cells were isolated. Total RNA was extracted and mRNA was purified. DNA microarray technique with 12 848 genes was used to analyze the gene expression profiles. Results The predicted 45 genes were enormously expressed in 21 patients with acute leukemia, which were consistent with the ALL and AML classification standards reported by Golub and others. 7 genes which were overexpressed in multiple-resistant cell line K562-n/VCR were also overexpressed in 6 cases of refractory acute leukemia. Further analysis showed that 31 genes were upregulated in AML (M_4-M_6) and ALL but downregulated in AML (M_1-M_3). Conclusion This results support the standard Golub has put forward. The reason that adult patients with ALL and subtypes of AML (M_4-M_6) have poorer prognosis in comparison with AMLM_1-M_3 is attributed to alterations in gene expression. Primary drug resistance may be the major characteristics of refractory leukemia. Analysis of gene expression profile in acute leukemia is significant for classification and prognosis.