Deep hematologic response to RD treatment in patients with multiple myeloma is associated with overexpression of IL-17R in CD138+ plasma cells.
Humans
Multiple Myeloma
/ drug therapy
Dexamethasone
/ pharmacology
Female
Male
Lenalidomide
/ pharmacology
Receptors, Interleukin-17
/ metabolism
Middle Aged
Aged
Plasma Cells
/ metabolism
Gene Expression Regulation, Neoplastic
/ drug effects
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Bone marrow microenvironment
Good response to therapy
IL-17
Immune response
Lenalidomide
Multiple myeloma
Tumor niche
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 10 2024
09 10 2024
Historique:
received:
09
04
2024
accepted:
26
09
2024
medline:
10
10
2024
pubmed:
10
10
2024
entrez:
9
10
2024
Statut:
epublish
Résumé
Lenalidomide (LEN) is widely used immunomodulatory drug (IMiD). Nonetheless, despite its efficacy, over time patients become resistant to LEN and relapse. Due to high clinical relevance, drug resistance in MM is being thoroughly investigated. However, less is known about predictors of good response to LEN-based treatment. The aim of this study was to identify molecular pathways associated with good and long response to LEN. The study included newly diagnosed MM patients (NDMM) and MM patients treated with first-line LEN and dexamethasone (RD) who achieved and least very good partial remission (VGPR). RNA was isolated from MM cells and new-generation sequencing was performed. Obtained results were validated with qRT-PCR. A global increase in gene expression was found in the RD group compared to NDMM, suggesting the involvement of epigenetic mechanisms. Moreover, upregulation of genes controlling the interaction within MM niche was detected. Next, genes controlling immune response were upregulated. In particular, the gene encoding the IL-17 receptor was overexpressed in the RD group which is a novel finding. This should be emphasized because IL-17-related signaling can potentially be targeted, providing the rationale for future research. Establishing the molecular background associated with long-lasting and profound response to LEN may improve LEN-based chemotherapy regimens and facilitate the development of adjuvant therapies to enhance its anti-MM activity.
Identifiants
pubmed: 39384864
doi: 10.1038/s41598-024-74558-3
pii: 10.1038/s41598-024-74558-3
doi:
Substances chimiques
Dexamethasone
7S5I7G3JQL
Lenalidomide
F0P408N6V4
Receptors, Interleukin-17
0
IL17RA protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
23559Subventions
Organisme : Narodowe Centrum Nauki
ID : 2023/07/X/NZ5/00051
Informations de copyright
© 2024. The Author(s).
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