The transcription factor NFE2 enhances expression of the hematopoietic master regulators SCL/TAL1 and GATA2

•NFE2 regulates GATA2 and SCL/TAL1 expression.•One mechanism by which elevated NFE2 contributes to MPN phenotype SCL/TAL1 and GATA2 are aberrantly overexpressed in primary MPN cells.•NFE2 induced GATA2 and SCL/TAL1 expression might contribute to MPN phenotype. 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.