Altered NFE2 activity predisposes to leukemic transformation and myelosarcoma with AML-specific aberrations

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Item Type:	Article
Title:	Altered NFE2 activity predisposes to leukemic transformation and myelosarcoma with AML-specific aberrations
Creators Name:	Jutzi, J.S., Basu, T., Pellmann, M., Kaiser, S., Steinemann, D., Sanders, M.A., Hinai, A.S.A., Zeilemaker, A., Bojtine Kovacs, S., Koellerer, C., Ostendorp, J., Aumann, K., Wang, W., Raffoux, E., Cassinat, B., Bullinger, L., Schlegelberger, B., Valk, P.J.M. and Pahl, H.L.
Abstract:	In acute myeloid leukemia (AML), acquired genetic aberrations carry prognostic implications and guide therapeutic decisions. Clinical algorithms have been improved by the incorporation of novel aberrations. Here, we report the presence and functional characterization of mutations in the transcription factor NFE2 in patients with AML and in a patient with myelosarcoma. We previously described NFE2 mutations in patients with myeloproliferative neoplasms and demonstrated that expression of mutant NFE2 in mice causes a myeloproliferative phenotype. Now, we show that, during follow-up, 34% of these mice transform to leukemia presenting with or without concomitant myelosarcomas, or develop isolated myelosarcomas. These myelosarcomas and leukemias acquired AML-specific alterations, including the murine equivalent of trisomy 8, loss of the AML commonly deleted region on chromosome 5q, and mutations in the tumor suppressor Our data show that mutations in NFE2 predispose to the acquisition of secondary changes promoting the development of myelosarcoma and/or AML.
Keywords:	Neoplastic Cell Transformation, Chromosome Aberrations, Acute Myeloid Leukemia, Mutation, p45 Subunit NF-E2 Transcription Factor, Myeloid Sarcoma, Tumor Suppressor Protein p53, Animals, Mice
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	133
Number:	16
Page Range:	1766-1777
Date:	18 April 2019
Official Publication:	https://doi.org/10.1182/blood-2018-09-875047
PubMed:	View item in PubMed

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