Aref Salah, Al Khodary Tawfik, Zeed Tarek Abou, El Sadiek Amre, El Menshawy Nadia, Al Ashery Rasha
Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura Cancer Institute, Mansoura, Egypt.
Medical Oncology Unit, Mansoura Faculty of Medicine, Mansoura Cancer Institute, Mansoura, Egypt.
Indian J Hematol Blood Transfus. 2015 Mar;31(1):21-8. doi: 10.1007/s12288-014-0395-z. Epub 2014 May 1.
Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). About 45 % of de novo adult AML and 20 % of pediatric AML lack cytogenetic abnormalities, so identification of predictive molecular markers might improve therapy. Mutation status of FLT3, NPM1 genes and gene expression levels of ERG, BAALC have been postulated as possible prognostic markers in pediatric AML with normal karyotype. Pretreatment blood samples from 47 cytogenetically normal AML patients were analysed for BAALC and ERG expression using real time RT-PCR. The patients were dichotomized at BAALC and ERG mean expression into low and high expression based on the median expression as cutoff. BAALC showed high expression in (24/47; 51.1 %) of patients and ERG high expression was detected in (22/47; 46.6 %). With follow-up for 1 year, patients with high BAALC and high ERG had inferior EFS (P = 0.001, P = 0.017 respectively), overall survival (P = 0.001, 0.08 respectively), and low rates of induction remission (P = 0.001, P = 0.0017 respectively) as compared to those with low expression. Also there was significant positive association between high expression of BAALC; ERG and FLT-ITD mutations (P = 0.016; P = 0.007 respectively). Multivariable analysis confirmed that high BAALC expression is an independent risk factor for EFS [HR for EFS 1.9(1.04-3.46) P = 0.037]; and OS [HR OS 1.55(1.7-3.36) P = 0.03].
Over expression of BAALC could predict adverse clinical outcome and may define important risk factor in cytogenetically normal pediatric AML.
细胞遗传学异常是急性髓系白血病（AML）的重要预后因素。约45%的成人初发AML和20%的儿童AML缺乏细胞遗传学异常，因此识别预测性分子标志物可能会改善治疗。FLT3、NPM1基因的突变状态以及ERG、BAALC的基因表达水平已被假定为核型正常的儿童AML中可能的预后标志物。使用实时RT-PCR分析了47例细胞遗传学正常的AML患者的预处理血样中BAALC和ERG的表达。根据中位数表达作为临界值，将患者按BAALC和ERG的平均表达分为低表达和高表达两组。BAALC在（24/47；51.1%）的患者中高表达，ERG高表达在（22/47；46.6%）的患者中被检测到。随访1年，与低表达患者相比，BAALC高表达和ERG高表达的患者无事件生存期（EFS）较差（分别为P = 0.001，P = 0.017）、总生存期（分别为P = 0.001，0.08）以及诱导缓解率较低（分别为P = 0.001，P = 0.0017）。此外，BAALC、ERG的高表达与FLT-ITD突变之间存在显著正相关（分别为P = 0.016；P = 0.007）。多变量分析证实，BAALC高表达是EFS的独立危险因素[EFS的风险比（HR）为1.9(1.04 - 3.46)，P = 0.037]；以及总生存期（OS）的独立危险因素[OS的HR为1.55(1.7 - 3.36)，P = 0.03]。
BAALC的过表达可预测不良临床结局，并且可能是细胞遗传学正常的儿童AML中的重要危险因素。
