The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Br J Haematol. 2020 Aug;190(4):495-507. doi: 10.1111/bjh.16534. Epub 2020 Feb 21.
Recent advances in sequencing technologies have allowed for the identification of recurrent mutations in acute myeloid leukaemia (AML). The transcription factor CCAAT enhancer binding protein alpha (CEBPA) is frequently mutated in AML, and biallelic CEBPA-mutant AML was recognised as a separate disease entity in the recent World Health Organization classification. However, CEBPA mutations are co-occurring with other aberrations in AML, and together these lesions form the clonal hierarchy that comprises the leukaemia in the patient. Here, we aim to review the current understanding of co-occurring mutations in CEBPA-mutated AML and their implications for disease biology and clinical outcome. We will put emphasis on patterns of cooperation, how these lesions cooperate with CEBPA mutations and the underlying potential molecular mechanisms. Finally, we will relate this to patient outcome and future options for personalised medicine.
近年来，测序技术的进步使得人们能够鉴定出急性髓系白血病（AML）中的反复突变。转录因子 CCAAT 增强子结合蛋白α（CEBPA）在 AML 中经常发生突变，双等位基因突变的 AML 在最近的世界卫生组织分类中被认为是一种独立的疾病实体。然而，CEBPA 突变与 AML 中的其他异常同时发生，这些病变共同构成了患者白血病中的克隆层次结构。在这里，我们旨在回顾 CEBPA 突变的 AML 中同时发生的突变及其对疾病生物学和临床结果的影响。我们将重点介绍合作模式，这些病变如何与 CEBPA 突变合作以及潜在的潜在分子机制。最后，我们将其与患者的预后和个性化医学的未来选择联系起来。
