The histone demethylase JMJD2C constitutes a novel NFE2 target gene that is required for the survival of JAK2V617F 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 for transformation to acute leukemia. Transgenic mice overexpressing NFE2 as well as mice harboring NFE2 mutati...

Full description

Saved in:
Bibliographic Details
Published in:Leukemia 2023-04, Vol.37 (4), p.919-923
Main Authors: Staehle, Anne Marie, Peeken, Jan Caspar, Vladimirov, Georg, Hoeness, Mirjam Elisabeth, Bojtine Kovacs, Sarolta, Karantzelis, Nikolaos, Gruender, Albert, Koellerer, Christoph, Jutzi, Jonas Samuel, Pahl, Heike Luise, Staehle, Hans Felix
Format: Article
Language:English
Subjects:
13/106
13/109
13/2
13/31
13/89
14/63
38/1
38/23
38/70
64/60
692/308/2778
692/308/575
692/699/1541/1990/2331
Binding sites
Cancer Research
Cell proliferation
Critical Care Medicine
Gene expression
Genes
Genetic transformation
Hematology
Histones
Intensive
Internal Medicine
Investigations
Letter
Leukemia
Medicine
Medicine & Public Health
Molecular modelling
Mutation
Neoplasms
Oncology
Pathophysiology
Phenotypes
Plasmids
Protein expression
Proteins
Therapeutic targets
Transgenic animals
Transgenic mice
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 JAK2 V617F 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.
ISSN:0887-6924
1476-5551
DOI:10.1038/s41375-023-01826-y