Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Blood. 2010 Dec 16;116(25):5660-9. doi: 10.1182/blood-2010-06-290536. Epub 2010 Sep 14.
BAALC and ERG expression levels are prognostic markers in younger (< 60 years) cytogenetically normal acute myeloid leukemia (CN-AML) adults; their prognostic impact in older (≥ 60 years) patients requires further investigation. We evaluated pretreatment expression of BAALC and ERG in 158 de novo patients treated on cytarabine/daunorubicin-based protocols. The patients were also characterized for other established molecular prognosticators. Low BAALC and ERG expression levels were associated with better outcome in univariable and multivariable analyses. Expression levels of both BAALC and ERG were the only factors significantly associated with overall survival upon multivariable analysis. To gain biological insights, we derived gene expression signatures associated with BAALC and ERG expression in older CN-AML patients. Furthermore, we derived the first microRNA expression signatures associated with the expression of these 2 genes. In low BAALC expressers, genes associated with undifferentiated hematopoietic precursors and unfavorable outcome predictors were down-regulated, whereas HOX genes and HOX-gene-embedded microRNAs were up-regulated. Low ERG expressers presented with down-regulation of genes involved in the DNA-methylation machinery, and up-regulation of miR-148a, which targets DNMT3B. We conclude that in older CN-AML patients, low BAALC and ERG expression associates with better outcome and distinct gene and microRNA expression signatures that could aid in identifying new targets and novel therapeutic strategies for older patients.
BAALC 和 ERG 的表达水平是年轻(<60 岁)细胞遗传学正常急性髓细胞白血病(CN-AML)成人的预后标志物;它们在老年(≥60 岁)患者中的预后影响需要进一步研究。我们评估了 158 例接受基于阿糖胞苷/柔红霉素方案治疗的初治患者的预处理 BAALC 和 ERG 表达。还对其他已建立的分子预后标志物对患者进行了特征描述。单变量和多变量分析均显示,低 BAALC 和 ERG 表达水平与更好的预后相关。多变量分析显示,BAALC 和 ERG 的表达水平是唯一与总生存期显著相关的因素。为了获得生物学见解,我们在老年 CN-AML 患者中推导了与 BAALC 和 ERG 表达相关的基因表达特征。此外,我们还推导了与这 2 个基因表达相关的第一个 microRNA 表达特征。在低 BAALC 表达者中,与未分化造血前体和不利预后预测因子相关的基因下调,而 HOX 基因和 HOX 基因嵌入的 microRNAs 上调。低 ERG 表达者表现为参与 DNA 甲基化机制的基因下调,以及 miR-148a 的上调,后者靶向 DNMT3B。我们得出结论,在老年 CN-AML 患者中,低 BAALC 和 ERG 表达与更好的预后相关,并具有独特的基因和 microRNA 表达特征,这可能有助于确定老年患者的新靶点和新治疗策略。