Roman-Gomez Jose, Jimenez-Velasco Antonio, Agirre Xabier, Prosper Felipe, Heiniger Anabel, Torres Antonio
Hematology Department, Reina Sofia Hospital, Avda, Menendez Pidal s/n, 14004 Cordoba, Spain.
J Clin Oncol. 2005 Oct 1;23(28):7043-9. doi: 10.1200/JCO.2005.01.4944.
To examine cancer genes undergoing epigenetic inactivation in a set of T-cell acute lymphoblastic leukemias (T-ALLs) to obtain the CpG island methylator phenotype (CIMP) in the disease and its possible correlation with clinical features and outcome of the patients.
Methylation-specific polymerase chain reaction was used to analyze methylation of the ADAMTS-1, ADAMTS-5, APAF-1, ASPP-1, CDH1, CDH13, DAPK, DIABLO, DKK-3, LATS-1, LATS-2, NES-1, p14, p15, p16, p57, p73, PARK-2, PTEN, sFRP1/2/4/5, SHP-1, SYK, TMS-1, and WIF-1 genes in samples from 50 consecutive T-ALL patients (19 children and 31 adults). Results were compared with results obtained in 286 B-cell acute lymphoblastic leukemias (B-ALLs).
A total of 88% of the T-ALL samples had at least one gene methylated. According to the number of methylated genes observed in each individual sample, 12 patients (24%) were included in the CIMP- group (zero to two methylated genes), and 38 patients (76%) were included in the CIMP+ group (> two methylated genes). Clinical features and remission rate did not differ significantly among both groups of patients. Estimated disease-free survival (DFS) rate at 12 years and overall survival (OS) rate at 13 years were 100% and 91% for the CIMP- group and 20% and 17% for the CIMP+ group, respectively (P = .0006 and P = .003, respectively). Multivariate analysis demonstrated that methylation profile was an independent prognostic factor in predicting DFS (P = .05) and OS (P = .02). A group of five genes (SYK-1, ASPP-1, sFRP-2, sFRP-5, and WIF-1) showed specificity for T-ALL compared with B-ALL.
Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in T-ALL.
检测一组T细胞急性淋巴细胞白血病（T-ALL）中发生表观遗传失活的癌症基因，以获得该疾病的CpG岛甲基化表型（CIMP）及其与患者临床特征和预后的可能相关性。
采用甲基化特异性聚合酶链反应分析50例连续T-ALL患者（19例儿童和31例成人）样本中ADAMTS-1、ADAMTS-5、APAF-1、ASPP-1、CDH1、CDH13、DAPK、DIABLO、DKK-3、LATS-1、LATS-2、NES-1、p14、p15、p16、p57、p73、PARK-2、PTEN、sFRP1/2/4/5、SHP-1、SYK、TMS-1和WIF-1基因的甲基化情况。将结果与286例B细胞急性淋巴细胞白血病（B-ALL）的结果进行比较。
总共88%的T-ALL样本至少有一个基因发生甲基化。根据每个个体样本中观察到的甲基化基因数量，12例患者（24%）被纳入CIMP-组（0至2个甲基化基因），38例患者（76%）被纳入CIMP+组（>2个甲基化基因）。两组患者的临床特征和缓解率无显著差异。CIMP-组12年的估计无病生存率（DFS）和13年的总生存率（OS）分别为100%和91%，CIMP+组分别为20%和17%（P分别为0.0006和0.003）。多因素分析表明，甲基化谱是预测DFS（P = 0.05）和OS（P = 0.02）的独立预后因素。与B-ALL相比，一组五个基因（SYK-1、ASPP-1、sFRP-2、sFRP-5和WIF-1）对T-ALL具有特异性。
我们的结果表明，甲基化谱可能是T-ALL中一种潜在的新的风险预测生物标志物。
