Baldus Claudia D, Mrózek Krzysztof, Marcucci Guido, Bloomfield Clara D
Department of Haematology and Oncology, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Br J Haematol. 2007 Jun;137(5):387-400. doi: 10.1111/j.1365-2141.2007.06566.x.
Normal cytogenetics are detected pretreatment in approximately 45% of patients with de novo acute myeloid leukaemia (AML); thus this constitutes the single largest cytogenetic group of AML. Recently, molecular genetic alterations with prognostic significance have been reported in these patients. They include internal tandem duplication of the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA and NPM1 genes and aberrant expression of the BAALC, ERG and MN1 genes. Additionally, gene-expression profiling has been applied to identify prognostically relevant subgroups. Substantial progress has been made in the understanding of molecular pathways deregulated in leukaemogenesis and how these defects can be targeted by novel therapeutic compounds. Here we critically review the molecular heterogeneity among AML patients with normal cytogenetics and discuss how these data may translate into a prognostic, molecular-based treatment stratification that may improve the currently unsatisfactory outcome of these patients.
在初发急性髓系白血病（AML）患者中，约45%在预处理时检测到正常细胞遗传学结果；因此，这构成了AML中最大的单一细胞遗传学组。最近，已报道这些患者存在具有预后意义的分子遗传学改变。它们包括FLT3基因的内部串联重复、MLL基因的部分串联重复、CEBPA和NPM1基因的突变以及BAALC、ERG和MN1基因的异常表达。此外，基因表达谱分析已被用于识别具有预后相关性的亚组。在理解白血病发生过程中失调的分子途径以及如何用新型治疗化合物靶向这些缺陷方面已取得了实质性进展。在此，我们对具有正常细胞遗传学的AML患者中的分子异质性进行批判性综述，并讨论这些数据如何转化为基于分子的预后治疗分层，这可能改善这些患者目前不尽人意的治疗结果。
