Institute of Hematology, University of Perugia, Perugia, Italy.
Blood Rev. 2013 Jan;27(1):13-22. doi: 10.1016/j.blre.2012.11.001. Epub 2012 Dec 20.
Acute myeloid leukemia (AML) is a molecularly heterogeneous disease. Based on cytogenetics and FISH, AML patients are stratified into three major risk categories: favourable, intermediate and unfavourable. However, prognostic stratification and treatment decision for the intermediate risk category, that mostly comprises AML patients with normal cytogenetics (CN-AML), has been difficult due to the clinical heterogeneity and scarce knowledge of the molecular alterations underlying this large AML subgroup. During the past decade, the identification of several mutations associated with CN-AML has resulted into important advances in the AML field. In this review, we address the biological features of the main mutations associated with CN-AML and the impact of next generation sequencing studies in expanding our knowledge of the molecular landscape of CN-AML. In addition, we outline the prognostic value of mutations for risk stratification of CN-AML patients and discuss the potential of mutations discovery process for developing new molecular targeted therapies.
急性髓系白血病（AML）是一种分子异质性疾病。基于细胞遗传学和 FISH，AML 患者被分为三个主要危险类别：预后良好、预后中等和预后不良。然而，由于中间风险类别（主要包括具有正常细胞遗传学的 AML 患者）的临床异质性和对其主要亚组 AML 分子改变的了解甚少，其预后分层和治疗决策一直具有挑战性。在过去十年中，与 CN-AML 相关的几种突变的鉴定在 AML 领域取得了重要进展。在这篇综述中，我们将讨论与 CN-AML 相关的主要突变的生物学特征，以及下一代测序研究在扩展我们对 CN-AML 分子景观的认识方面的作用。此外，我们概述了突变对 CN-AML 患者风险分层的预后价值，并讨论了突变发现过程在开发新的分子靶向治疗方面的潜力。
