The histone demethylase JMJD2C constitutes a novel NFE2 target gene that is required for the survival of JAK2^V617F mutated cells

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 them for transformation to acute leukaemia. Transgenic mice overexpressing NFE2 and harbouring NFE2 mutations display an MPN phenotype and spontaneously develop leukaemia. However, the molecular mechanisms effecting NFE2-driven leukemic transformation remain incompletely understood. The study showed that the pro-leukemic histone demethylase JMJD2C constitutes a novel NFE2 target gene. JMJD2C expression is elevated in MPN patients and NFE2 transgenic mice. Moreover, the loss of JMJD2C selectively impairs the proliferation of JAK2V617F mutated cells. The data suggest that JMJD2C represents a promising drug target in MPN and provide a rationale for further investigation in preclinical and clinical settings.