Outcome modeling with CRLF2, IKZF1, JAK and minimal residual disease Study in pediatric acute lymphoblastic leukemia: a Children's Oncology Group
Outcome modeling with CRLF2, IKZF1, JAK and minimal residual disease Study in pediatric acute lymphoblastic leukemia: a Children's Oncology Group
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DOI：
10.1182/blood-2011-11-394221
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发表时间：
2012-04-12
期刊：
影响因子：
20.3
通讯作者：
Willman, Cheryl L.
中科院分区：
文献类型：
--
作者：
Chen, I. Ming;Harvey, Richard C.;Willman, Cheryl L.
由于关于儿童 B 前体 ALL 分类为标准/中危 (SR) 或高危 (HR) 中 CRLF2 基因组重排的预后意义存在争议，我们评估了 CRLF2 mRNA 表达、CRLF2 基因组病变（IGH@-CRLF2、P2RY8-CRLF2、CRLF2）的预后意义。 F232C），COG 试验 P9905/P9906 中 1,061 名儿科 ALL 患者（499 HR 和 562 SR）中经常与高 CRLF2 表达（IKZF1、JAK、IL7R）和微小残留病（MRD）相关的基因缺失/突变。而 17.5% 的病例（19%）中发现了非常高的 CRLF2 表达。 HR，SR的16.2%），只有51.4%的高CRLF2表达者有CRLF2基因组病变。在缺乏已知基因组损伤的病例中，CRLF2 表达升高的机制仍有待确定。所有 CRLF2 基因组损伤和几乎所有 JAK 突变都在高 CRLF2 表达者中发现，而 IKZF1 缺失/突变分布在整个队列中。多变量分析、NCI 风险组、MRD、CRLF2 高表达（每个 P
As controversy exists regarding the prognostic significance of genomic rearrangements ofCRLF2 in pediatric B-precursor ALL classified as standard/intermediate-risk (SR) or high-risk(HR), we assessed the prognostic significance of CRLF2 mRNA expression, CRLF2 genomiclesions (IGH@-CRLF2, P2RY8-CRLF2, CRLF2 F232C), deletion/mutation in genes frequentlyassociated with high CRLF2 expression (IKZF1, JAK, IL7R) and minimal residual disease(MRD) in 1,061 pediatric ALL patients (499 HR and 562 SR) on COG Trials P9905/P9906.While very high CRLF2 expression was found in 17.5% of cases (19% of HR, 16.2% of SR),only 51.4% of high CRLF2-expressors had CRLF2 genomic lesions. The mechanism underlyingelevated CRLF2 expression in cases lacking known genomic lesions remains to be determined.All CRLF2 genomic lesions and virtually all JAK mutations were found in high CRLF2-expressors, while IKZF1 deletions/mutations were distributed across the full cohort. Inmultivariate analyses, NCI risk group, MRD, high CRLF2 expression (each P