文章：

早期T细胞前体白血病的临床和分子特征：成人T-ALL中FLT3突变频率高的高危亚群

Clinical and molecular characterization of early T-cell precursor leukemia: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations

原文发布日期：2012-01-27

DOI: 10.1038/bcj.2011.49

类型: Original Article

开放获取: 是

英文摘要：

A subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was characterized by a gene expression profile comparable to that of early T-cell precursors (ETPs) with a highly unfavorable outcome. We have investigated clinical and molecular characteristics of the ETP-ALL subgroup in adult T-ALL. As ETP-ALL represents a subgroup of early T-ALL we particularly focused on this cohort and identified 178 adult patients enrolled in the German Acute Lymphoblastic Leukemia Multicenter studies (05/93–07/03). Of these, 32% (57/178) were classified as ETP-ALL based on their characteristic immunophenotype. The outcome of adults with ETP-ALL was poor with an overall survival of only 35% at 10 years, comparable to the inferior outcome of early T-ALL with 38%. The molecular characterization of adult ETP-ALL revealed distinct alterations with overexpression of stem cell-related genes (BAALC, IGFBP7, MN1, WT1). Interestingly, we found a low rate of NOTCH1 mutations and no FBXW7 mutations in adult ETP-ALL. In contrast, FLT3 mutations, rare in the overall cohort of T-ALL, were very frequent and nearly exclusively found in ETP-ALL characterized by a specific immunophenotype. These molecular characteristics provide biologic insights and implications with respect to innovative treatment strategies (for example, tyrosine kinase inhibitors) for this high-risk subgroup of adult ETP-ALL.

摘要翻译： 

儿童急性T淋巴母细胞白血病（T-ALL）的一个亚群具有与早期T细胞前体（ETP）相似的基因表达特征，预后极差。我们研究了成人T-ALL中ETP-ALL亚组的临床和分子特征。由于ETP-ALL属于早期T-ALL的一个亚组，我们重点分析了该队列，共纳入德国急性淋巴细胞白血病多中心研究（05/93–07/03）中的178例成人患者。其中32%（57/178）根据特征性免疫表型被归类为ETP-ALL。成人ETP-ALL的预后很差，10年总生存率仅为35%，与早期T-ALL的38%相似。成人ETP-ALL的分子特征显示其具有独特的改变，包括干细胞相关基因（BAALC、IGFBP7、MN1、WT1）的过表达。有趣的是，我们发现成人ETP-ALL中NOTCH1突变率低，且未检测到FBXW7突变。相比之下，在整个T-ALL队列中罕见的FLT3突变在ETP-ALL中非常常见，且几乎仅见于具有特定免疫表型的ETP-ALL。这些分子特征为这一成人ETP-ALL高危亚组提供了生物学见解，并对创新治疗策略（例如酪氨酸激酶抑制剂）具有重要启示。

原文链接：

Clinical and molecular characterization of early T-cell precursor leukemia: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations