Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Level 5, Sir James Spence Institute, Royal Victoria Infirmary, Queen Victoria Rd, Newcastle-upon-Tyne, NE1 4LP, United Kingdom.
J Clin Oncol. 2012 Sep 1;30(25):3100-8. doi: 10.1200/JCO.2011.40.3907. Epub 2012 Jul 30.
To determine the prevalence and prognostic impact of significant acute lymphoblastic leukemia (ALL) -related genes: CRLF2 deregulation (CRLF2-d), IGH@ translocations (IGH@-t), and deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1, and EBF1 in adolescents and adults.
The cohort comprised 454 patients (age 15 to 60 years old) treated on the multicenter United Kingdom Acute Lymphoblastic Leukaemia Trial XII/Eastern Cooperative Oncology Group 2993 trial (UKALLXII/ECOG2993) with Philadelphia-negative B-cell precursor ALL. Fluorescent in situ hybridization and multiplex ligation-dependent probe amplification were used to detect these genetic alterations.
Twenty patients (5%) had CRLF2-d (P2RY8-CRLF2, n = 7; IGH@-CRLF2, n = 13), and 36 patients (8%) harbored an IGH@-t with a different partner gene. There was little overlap between IGH@-t, CRLF2-d, and established chromosomal abnormalities. Deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1, or EBF1 were prevalent with 101 (33%) of 304 patients harboring one and 102 (33%) harboring two or more alterations, occurring with varying frequency in all cytogenetic subgroups. The 5-year event-free survival, relapse-free survival (RFS), and overall survival (OS) rates for the whole cohort were 40%, 55%, and 43%, respectively. Patients with CRLF2-d, IGH@-t, and IKZF1 deletions were associated with an inferior outcome in univariate but not multivariate analysis. In particular, CRLF2-d patients had a lower RFS compared with other patients (30%), whereas those with IGH@-t or IKZF1 deletions had a lower OS (27% and 35%, respectively).
CRLF2-d and IGH@-t represent distinct subtypes of adolescent and adult ALL. Deletions of key B-cell differentiation and cell cycle control genes are highly prevalent but vary in frequency by cytogenetic subgroup. CRLF2-d, IGH@-t, and IKZF1 deletions are associated with poor outcome in adolescent and adult ALL.
确定重大急性淋巴细胞白血病（ALL）相关基因的发生率和预后影响：CRLF2 失调（CRLF2-d）、IGH@易位（IGH@-t）以及 CDKN2A/B、IKZF1、PAX5、ETV6、RB1、BTG1 和 EBF1 的缺失。
该队列包括 454 名（年龄 15 至 60 岁）接受多中心英国急性淋巴细胞白血病试验 XII/东部合作肿瘤学组 2993 试验（UKALLXII/ECOG2993）治疗的费城阴性 B 细胞前体 ALL 患者。荧光原位杂交和多重连接依赖性探针扩增用于检测这些遗传改变。
20 名患者（5%）存在 CRLF2-d（P2RY8-CRLF2，n=7；IGH@-CRLF2，n=13），36 名患者（8%）携带不同伙伴基因的 IGH@-t。IGH@-t、CRLF2-d 和既定染色体异常之间几乎没有重叠。CDKN2A/B、IKZF1、PAX5、ETV6、RB1、BTG1 或 EBF1 的缺失较为常见，304 名患者中有 101 名（33%）携带一种缺失，102 名（33%）携带两种或更多缺失，在所有细胞遗传学亚组中发生频率不同。整个队列的 5 年无事件生存率、无复发生存率（RFS）和总生存率（OS）分别为 40%、55%和 43%。在单变量分析中，存在 CRLF2-d、IGH@-t 和 IKZF1 缺失的患者预后较差，但在多变量分析中并非如此。特别是，与其他患者（30%）相比，存在 CRLF2-d 的患者 RFS 较低，而存在 IGH@-t 或 IKZF1 缺失的患者 OS 较低（分别为 27%和 35%）。
CRLF2-d 和 IGH@-t 代表青少年和成人 ALL 的不同亚型。关键 B 细胞分化和细胞周期控制基因的缺失非常普遍，但在细胞遗传学亚组中频率不同。CRLF2-d、IGH@-t 和 IKZF1 缺失与青少年和成人 ALL 的不良预后相关。
