RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response

Autor: E. De Bruyne, Lucienne Michaux, Cecilia Mancini, Iwona Wlodarska, Karin Vanderkerken, H Lemmens, Emanuela Garelli, Pieter Sonneveld, Isabel J.F. Hofman, Ellen Geerdens, Michel Delforge, M. van Duin, Anna Aspesi, K. De Keersmaecker, Laura Fancello, George Mulligan, Peter Vandenberghe
Přispěvatelé: Hematology, Basic (bio-) Medical Sciences
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Proto-Oncogenes/genetics
Bortezomib
Fusion gene
0302 clinical medicine
Hematology
Anesthesiology and Pain Medicine
Genes
Tumor Suppressor
Multiple myeloma
education.field_of_study
RNA
Messenger/analysis
DNA-Binding Proteins
Leukemia
Oncology
Chromosomes
Human
Pair 1
030220 oncology & carcinogenesis
Chromosomal region
Bortezomib/therapeutic use
Chromosome Deletion
Multiple Myeloma
medicine.drug
Ribosomal Proteins
medicine.medical_specialty
Multiple Myeloma/drug therapy
Transcription Factors/genetics
Antineoplastic Agents
Article
Ribosomal protein L5
03 medical and health sciences
Internal medicine
Proto-Oncogenes
medicine
Humans
RNA
Messenger
education
business.industry
Antineoplastic Agents/therapeutic use
medicine.disease
MDS1 and EVI1 Complex Locus Protein
Lymphoma
030104 developmental biology
Immunology
Cancer research
Ribosomal Proteins/genetics
mutation
business
DNA-Binding Proteins/genetics
Transcription Factors
Zdroj: Leukemia, 31(8), 1706-1714. Nature Publishing Group
Leukemia
ISSN: 1476-5551
0887-6924
Popis: Chromosomal region 1p22 is deleted in ≥20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression. Interestingly, RPL5 but not EVI5 mRNA levels were significantly lower in relapsed patients responding to bortezomib and; both in newly diagnosed and relapsed patients, bortezomib treatment could overcome their bad prognosis by raising their progression-free survival to equal that of patients with high RPL5 expression. In conclusion, our genetic data restrict the MDR on 1p22 to EVI5 and RPL5 and although the role of these genes in promoting MM progression remains to be determined, we identify RPL5 mRNA expression as a biomarker for initial response to bortezomib in relapsed patients and subsequent survival benefit after long-term treatment in newly diagnosed and relapsed patients.
Databáze: OpenAIRE
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