PEG10 amplification at 7q21.3 potentiates large-cell transformation in cutaneous T-cell lymphoma.
Blood
; 139(4): 554-571, 2022 01 27.
Article
en En
| MEDLINE
| ID: mdl-34582557
ABSTRACT
Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, undergo large-cell transformation (LCT) in the late stage, manifesting aggressive behavior, resistance to treatments, and poor prognosis, but the mechanisms involved remain unclear. To identify the molecular driver of LCT, we collected tumor samples from 133 MF patients and performed whole-transcriptome sequencing on 49 advanced-stage MF patients, followed by integrated copy number inference and genomic hybridization. Tumors with LCT showed unique transcriptional programs and enriched expressions of genes at chr7q. Paternally expressed gene 10 (PEG10), an imprinted gene at 7q21.3, was ectopically expressed in malignant T cells from LCT, driven by 7q21.3 amplification. Mechanistically, aberrant PEG10 expression increased cell size, promoted cell proliferation, and conferred treatment resistance by a PEG10/KLF2/NF-κB axis in in vitro and in vivo models. Pharmacologically targeting PEG10 reversed the phenotypes of proliferation and treatment resistance in LCT. Our findings reveal new molecular mechanisms underlying LCT and suggest that PEG10 inhibition may serve as a promising therapeutic approach in late-stage aggressive T-cell lymphoma.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
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Transformación Celular Neoplásica
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Linfoma Cutáneo de Células T
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Proteínas de Unión al ARN
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Proteínas de Unión al ADN
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Proteínas Reguladoras de la Apoptosis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Blood
Año:
2022
Tipo del documento:
Article
País de afiliación:
China