Division of Molecular Hematology, Department of Internal Medicine, Hematology/Oncology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Division of Molecular Hematology, Department of Internal Medicine, Hematology/Oncology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Exp Hematol. 2020 Jul;87:42-47.e1. doi: 10.1016/j.exphem.2020.06.004. Epub 2020 Jun 25.
Activity of the transcription factor NFE2 is elevated in the majority of patients with myeloproliferative neoplasms (MPNs), either by overexpression of the wild-type alleles or by the presence of an activating mutation. In murine models, enhanced NFE2 activity causes an MPN phenotype with spontaneous transformation to acute leukemia. However, little is known about the downstream target genes activated by augmented NFE2 levels. Here, we describe that NFE2 regulates expression of the hematopoietic master regulators GATA2 and SCL/TAL1, which are in turn overexpressed in primary MPN cells, suggesting that concomitant aberrant activation of several transcription factors coordinately contributes to the cellular expansion characteristic of these disorders.
转录因子 NFE2 的活性在大多数骨髓增殖性肿瘤（MPNs）患者中升高，这要么是由于野生型等位基因的过表达，要么是由于存在激活突变。在小鼠模型中，增强的 NFE2 活性导致 MPN 表型，并自发转化为急性白血病。然而，人们对 NFE2 水平升高激活的下游靶基因知之甚少。在这里，我们描述了 NFE2 调节造血主调控因子 GATA2 和 SCL/TAL1 的表达，这些因子在原发性 MPN 细胞中过度表达，这表明几个转录因子的协同异常激活共同促成了这些疾病的细胞扩增特征。
