High WT1 mRNA expression after induction chemotherapy and FLT3-ITD have prognostic impact in pediatric acute myeloid leukemia: a study of the Japanese Childhood AML Cooperative Study Group
High WT1 mRNA expression after induction chemotherapy and FLT3-ITD have prognostic impact in pediatric acute myeloid leukemia: a study of the Japanese Childhood AML Cooperative Study Group
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DOI：
10.1007/s12185-012-1163-1
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发表时间：
2012-10-01
影响因子：
2.1
通讯作者：
Hayashi, Yasuhide
中科院分区：
文献类型：
--
作者：
Shimada, Akira;Taki, Tomohiko;Hayashi, Yasuhide
WT 1 mRNA表达在儿童急性髓细胞白血病（AML）中的预后价值仍存在争议。对来自日本儿童AML合作治疗方案AML 99的新诊断（n = 158）AML患者样本同时分析WT 1表达、细胞遗传学异常和基因改变（FLT 3、KIT、MLL和RAS）。在158份初始诊断性AML骨髓样本中的122份（77.8%）中检测到WT 1表达（包括超过2，500拷贝/μ gRNA）（中位数为45，500拷贝/μ gRNA）。在法裔美国人和英国人（FAB）-M0、M3、M7中检测到较高的WT 1表达，而在M4和M5中检测到较低的表达。AML伴inv（16）、t（15;17）和Down综合征患者WT 1表达增高，伴11 q23异常患者WT 1表达降低。多因素分析显示，FLT 3-内部串联重复（ITD）、KIT突变、MLL-部分串联重复与不良预后相关，而WT 1高表达与不良预后无关。FLT 3-ITD与WT 1表达和预后相关。此外，分析诱导化疗后74例WT 1表达。诱导化疗后WT 1高表达与M1或M2/M3骨髓、FLT 3-ITD及不良预后显著相关。74例AML患者的多变量分析显示，FLT 3-ITD、MLL-PTD和KIT突变与不良预后相关;然而，NRAS突变、KRAS突变和高WT 1表达（> 10，000拷贝/μ gRNA）并未显示不良预后。我们的研究结果表明，诊断时较高的WT 1表达与不良预后无关，但诱导化疗后的WT 1表达被认为是儿童AML临床结局的有用预测因子。
The prognostic value of WT1 mRNA expression in pediatric acute myeloid leukemia (AML) remains controversial. A sample of newly diagnosed (n = 158) AML patients from the Japanese Childhood AML Cooperative Treatment Protocol, AML 99, were simultaneously analyzed for WT1 expression, cytogenetic abnormalities and gene alterations (FLT3, KIT, MLL, and RAS). WT1 expression (including more than 2,500 copies/mu gRNA) was detected in 122 of the 158 (77.8 %) initial diagnostic AML bone marrow samples (median 45,500 copies/mu gRNA). Higher WT1 expression was detected in French American British (FAB)-M0, M3, M7 and lower expression in M4 and M5. Higher WT1 expression was detected in AML with inv(16), t(15;17) and Down syndrome and lower in AML with 11q23 abnormalities. Multivariate analyses demonstrated that FLT3-internal tandem duplication (ITD), KIT mutation, MLL-partial tandem duplication were correlated with poor prognosis; however, higher WT1 expression was not. FLT3-ITD was correlated with WT1 expression and prognosis. Furthermore, 74 WT1 expression after induction chemotherapy was analyzed. Higher WT1 expression after induction chemotherapy was significantly correlated with M1 or M2/M3 marrow, FLT3-ITD and poor prognosis. Multivariate analyses in 74 AML patients revealed that FLT3-ITD, MLL-PTD, and KIT mutations were associated with poor prognosis; however, NRAS Mutation, KRAS mutation and high WT1 expression (> 10,000 copies/mu gRNA) did not show poor prognosis. Our findings suggest that higher WT1 expression at diagnosis does not correlate with poor prognosis, but that WT1 expression after induction chemotherapy is considered to be a useful predictor of clinical outcome in pediatric AML.