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Altered NFE2 activity predisposes to leukemic transformation and myelosarcoma with AML-specific aberrations
- Source :
- Blood, 133(16), 1766-1777. American Society of Hematology
- Publication Year :
- 2019
- Publisher :
- American Society of Hematology, 2019.
-
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 Trp53. Our data show that mutations in NFE2 predispose to the acquisition of secondary changes promoting the development of myelosarcoma and/or AML.
- Subjects :
- Adult
Male
Myeloid
Adolescent
Immunology
Trisomy 8
medicine.disease_cause
Biochemistry
Mice
Young Adult
hemic and lymphatic diseases
Animals
Humans
Medicine
Sarcoma, Myeloid
Transcription factor
Aged
Aged, 80 and over
Chromosome Aberrations
Mutation
Myeloid Neoplasia
business.industry
Myeloid leukemia
Cell Biology
Hematology
Middle Aged
medicine.disease
Phenotype
Leukemia, Myeloid, Acute
Leukemia
Cell Transformation, Neoplastic
medicine.anatomical_structure
NF-E2 Transcription Factor, p45 Subunit
Cancer research
Female
Sarcoma
Tumor Suppressor Protein p53
business
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 133
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....0460b0c0e4f0250bf829b6853f991b84