NFE2转录因子在大多数骨髓增生性肿瘤（MPN）患者中过度表达。此外，在MPN患者的某个子集中发现的NFE2突变，强烈促使急性白血病的转化。过度表达NFE2的转基因小鼠以及携带NFE2突变的小鼠表现出MPN表型并自发产生白血病。然而，影响NFE2驱动的白血病转化的分子机制尚未完全理解。在这里，我们展示了亲白血病组织蛋白去甲基化酶JMJD2C构成了一种新的NFE2靶基因。JMJD2C表达在MPN患者以及NFE2转基因小鼠中升高。此外，我们展示了JMJD2C的丧失选择性地损伤JAK2V617F突变细胞的增殖。我们的数据表明，JMJD2C代表了MPN中一个有前途的药物靶标，并为进一步的临床前和临床研究提供了合理性。 ©2023。作者（们）

The transcription factor NFE2 is overexpressed in most patients with myeloproliferative neoplasms (MPN). Moreover, mutations in NFE2, found in a subset of MPN patients, strongly predispose for transformation to acute leukemia. Transgenic mice overexpressing NFE2 as well as mice harboring NFE2 mutations display an MPN phenotype and spontaneously develop leukemia. However, the molecular mechanisms effecting NFE2-driven leukemic transformation remain incompletely understood. Here we show that the pro-leukemic histone demethylase JMJD2C constitutes a novel NFE2 target gene. JMJD2C expression is elevated in MPN patients as well as in NFE2 transgenic mice. Moreover, we show that loss of JMJD2C selectively impairs proliferation of JAK2V617F mutated cells. Our data suggest that JMJD2C represents a promising drug target in MPN and provide a rationale for further investigation in preclinical and clinical settings.© 2023. The Author(s).