文章：

BAALC表达：细胞遗传学正常的急性髓性白血病预后危险分层和残留疾病检测的合适标志物

BAALC expression: a suitable marker for prognostic risk stratification and detection of residual disease in cytogenetically normal acute myeloid leukemia

原文发布日期：2014-01-10

DOI: 10.1038/bcj.2013.71

类型: Original Article

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英文摘要：

High brain and acute leukemia, cytoplasmic (BAALC) expression defines an important risk factor in cytogenetically normal acute myeloid leukemia (CN-AML). The prognostic value of BAALC expression in relation to other molecular prognosticators was analyzed in 326 CN-AML patients (<65 years). At diagnosis, high BAALC expression was associated with prognostically adverse mutations: FLT3 internal tandem duplication (FLT3-ITD) with an FLT3-ITD/FLT3 wild-type (wt) ratio of ⩾0.5 (P=0.001), partial tandem duplications within the MLL gene (MLL-PTD) (P=0.002), RUNX1 mutations (mut) (P<0.001) and WT1mut (P=0.001), while it was negatively associated with NPM1mut (P<0.001). However, high BAALC expression was also associated with prognostically favorable biallelic CEBPA (P=0.001). Survival analysis revealed an independent adverse prognostic impact of high BAALC expression on overall survival (OS) and event-free survival (EFS), and also on OS when eliminating the effect of allogeneic stem cell transplantation (SCT) (OSTXcens). Furthermore, we analyzed BAALC expression in 416 diagnostic and follow-up samples of 66 patients. During follow-up, BAALC expression correlated with mutational load or expression levels, respectively, of other minimal residual disease markers: FLT3-ITD (r=0.650, P<0.001), MLL-PTD (r=0.728, P<0.001), NPM1mut (r=0.599, P<0.001) and RUNX1mut (r=0.889, P<0.001). Moreover, a reduction in BAALC expression after the second cycle of induction chemotherapy was associated with improved EFS. Thus, our data underline the utility of BAALC expression as a marker for prognostic risk stratification and detection of residual disease in CN-AML.

摘要翻译： 

高脑和急性白血病胞质型（BAALC）表达是细胞遗传学正常急性髓系白血病（CN-AML）的重要风险因素。本研究在326例CN-AML患者（<65岁）中分析了BAALC表达相对于其他分子预后标志物的价值。诊断时，高BAALC表达与预后不良突变相关：FLT3内部串联重复（FLT3-ITD）且FLT3-ITD/FLT3野生型比率≥0.5（P=0.001）、MLL基因部分串联重复（MLL-PTD）（P=0.002）、RUNX1突变（P<0.001）及WT1突变（P=0.001），而与NPM1突变呈负相关（P<0.001）。但同时也与预后良好的双等位CEBPA突变相关（P=0.001）。生存分析显示，高BAALC表达对总生存期（OS）和无事件生存期（EFS）具有独立不良预后影响，在排除异基因干细胞移植（SCT）影响后的总生存期（OSTXcens）中亦然。此外，我们分析了66例患者的416份诊断及随访样本。随访期间，BAALC表达与其他微小残留病灶标志物的突变负荷或表达水平呈正相关：FLT3-ITD（r=0.650, P<0.001）、MLL-PTD（r=0.728, P<0.001）、NPM1突变（r=0.599, P<0.001）及RUNX1突变（r=0.889, P<0.001）。更重要的是，诱导化疗第二周期后BAALC表达水平下降与改善的EFS相关。因此，我们的数据证实了BAALC表达作为CN-AML预后风险分层和残留病灶检测标志物的临床应用价值。

原文链接：

BAALC expression: a suitable marker for prognostic risk stratification and detection of residual disease in cytogenetically normal acute myeloid leukemia