Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial
Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial
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DOI：
10.1182/blood-2010-07-297135
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发表时间：
2011-02-17
期刊：
影响因子：
20.3
通讯作者：
Moorman, Anthony V.
中科院分区：
文献类型：
--
作者：
Ensor, Hannah M.;Schwab, Claire;Moorman, Anthony V.
CRLF2(CRLF2-d) 的表达失调是通过与 IGH@ 增强子或 P2RY8 启动子并置而产生的。在接受 MRC ALL97 治疗的 865 名 BCP-ALL 儿童中，52 名 (6%) 患有 CRLF2-d，但在唐氏综合症患者中更为常见 (54%)。 P2RY8-CRLF2 (n = 43) 比 IGH@-CRLF2 (n = 9) 更常见。 CRLF2-d 与年龄、性别或白细胞计数无关，但 IGH@-CRLF2 患者比 P2RY8-CRLF2 患者年龄大（中位 8 岁 vs 4 岁，P = .0017）。 CRLF2-d 患者更有可能出现肝脏和脾脏肿大（38% vs 18%，P < .001）。 CRLF2-d 并未与已确定的染色体易位一起出现，但 6 例 (12%) 病例具有高度超二倍体，5 例 (10%) 具有 iAMP21。单变量分析表明 CRLF2-d 与较差的结果相关：（无事件生存 [EFS] 风险比 2.27 [95% 置信区间 1.48-3.47]，P < .001；OS 3.69 [2.34-5.84]，P < .001）。然而，多变量分析表明，其影响是由其他危险因素介导的，例如细胞遗传学和 DS 状态（EFS 1.45 [0.88-2.39]，P = .140；OS 1.90 [1.08-3.36]，P = .027）。尽管 IGH@-CRLF2 患者的预后似乎比 P2RY8-CRLF2 患者差，但结果并不显着（EFS 2.69 [1.15-6.31]，P = .023；OS 2.86 [1.15-6.79]，P = .021）。因此，我们得出结论，CRLF2-d患者应归入细胞遗传学中间风险组。 （血。2011；117（7）：2129-2136）
Deregulated expression of CRLF2(CRLF2-d) arises via its juxtaposition to the IGH@ enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47], P < .001; OS 3.69 [2.34-5.84], P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31], P = .023; OS 2.86 [1.15-6.79], P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group. (Blood. 2011; 117(7): 2129-2136)