Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliero-Universitaria Udine, Udine, Italy.
Am J Hematol. 2013 Oct;88(10):848-52. doi: 10.1002/ajh.23516. Epub 2013 Jul 23.
Overexpression of brain and acute leukemia cytoplasmic (BAALC) gene confers poor prognosis in cytogenetically normal acute myeloid leukemia (AML) patients, while less defined is its role in AML with abnormal karyotype. We evaluated the effect of BAALC overexpression on outcome of 175 adult AML patients with different cytogenetic risks. Karyotype was favorable in 13, intermediate in 117 and unfavorable in 45 patients, respectively. Quantitative BAALC expression was determined by real-time PCR, with cut off value set at 50th percentile. BAALC was overexpressed in 87/175 (50%) patients, without association with cytogenetic status. High BAALC was associated with unmutated NPM (P = 0.006) and CD34 positivity (P < 0.0001). Complete remission (CR) was attained in 111 patients (63%), and was maintained at 5 years in 52 ± 7%. BAALC overexpression had a negative impact on CR achievement (P = 0.04), while did not influence relapse probability. Median survival was 22 months with a 5-years overall survival (OS) of 35%. Factors with a negative impact on OS were older age (P = 0.0001), unfavorable cytogenetic (P = 0.005), ABCG2 overexpression (P = 0.03) and high BAALC levels (P = 0.01). We observed a worse outcome in patients with high BAALC expression through all cytogenetic risk categories: 5-years OS was 100% vs. 71% in patients with favorable cytogenetics (P = 0.05), 55% vs. 40% in cases with intermediate karyotype (P = 0.04) and 34% vs. 23% in unfavorable cytogenetic subgroup (P = 0.02). BAALC overexpression identified AML patients with poor prognosis in all cytogenetic groups. Though relatively rare, BAALC positivity in patients with favorable or unfavorable karyotype significantly worsened survival.
脑和急性髓系白血病细胞质（BAALC）基因的过度表达与核型正常的急性髓系白血病（AML）患者的不良预后相关，但其在核型异常的 AML 中的作用尚不明确。我们评估了 BAALC 过表达对 175 例不同细胞遗传学风险的成人 AML 患者结局的影响。核型分别为良好（13 例）、中等（117 例）和不良（45 例）。通过实时 PCR 确定 BAALC 的定量表达，以第 50 个百分位数作为截止值。175 例患者中有 87 例（50%）BAALC 过表达，与细胞遗传学状态无关。高 BAALC 与未突变的 NPM（P=0.006）和 CD34 阳性（P＜0.0001）相关。111 例患者（63%）获得完全缓解（CR），5 年时维持 CR 的比例为 52±7%。BAALC 过表达对 CR 获得有负面影响（P=0.04），但对复发率无影响。中位生存时间为 22 个月，5 年总生存率（OS）为 35%。对 OS 有负面影响的因素包括年龄较大（P=0.0001）、不良细胞遗传学（P=0.005）、ABCG2 过表达（P=0.03）和高 BAALC 水平（P=0.01）。我们观察到在所有细胞遗传学风险类别中，高 BAALC 表达患者的预后更差：核型良好的患者 5 年 OS 为 100%，核型中等的患者为 55%（P=0.05），核型不良的患者为 34%（P=0.02）。BAALC 过表达确定了所有细胞遗传学组中预后不良的 AML 患者。虽然相对罕见，但在核型良好或不良的患者中 BAALC 阳性显著降低了生存。
