A Single Nucleotide Polymorphism in
Adult
Aged
Combined Modality Therapy
Female
Gene Expression Regulation, Neoplastic
Genetic Association Studies
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Large Neutral Amino Acid-Transporter 1
/ genetics
Leukocytes, Mononuclear
/ drug effects
Male
Melphalan
/ administration & dosage
Middle Aged
Multiple Myeloma
/ drug therapy
Polymorphism, Single Nucleotide
Transplantation, Autologous
/ adverse effects
Treatment Outcome
Multiple myeloma
SLC7A5
clinical response
melphalan
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
29
11
2018
revised:
08
12
2018
accepted:
10
12
2018
entrez:
29
12
2018
pubmed:
29
12
2018
medline:
8
1
2019
Statut:
ppublish
Résumé
SLC7A5 is recognized as the major mediator of melphalan uptake into multiple myeloma (MM) cells; however, its contribution to the inter-patient variability of melphalan efficacy and toxicity is yet to be well elucidated. This study aimed to investigate the impact of a single nucleotide polymorphism (SNP) rs4240803 in SLC7A5 on the gene expression, ex vivo sensitivity to melphalan, and clinical outcomes in MM patients who were undergoing autologous stem cell transplantation with high-dose melphalan. Peripheral blood mononuclear cells (PBMC) were collected from 108 MM patients prior to melphalan therapy. Clinical data were also collected from these patients following melphalan therapy. rs4240803 was associated with elevated expression of SLC7A5 mRNA, higher ex vivo sensitivity to melphalan in PBMCs, and positive 90-day response in these patients (p=0.047, 0.10, 0.049, respectively). rs4240803 impacted the expression of SLC7A5, thus contributing to the clinical response of MM patients to melphalan therapy.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
SLC7A5 is recognized as the major mediator of melphalan uptake into multiple myeloma (MM) cells; however, its contribution to the inter-patient variability of melphalan efficacy and toxicity is yet to be well elucidated. This study aimed to investigate the impact of a single nucleotide polymorphism (SNP) rs4240803 in SLC7A5 on the gene expression, ex vivo sensitivity to melphalan, and clinical outcomes in MM patients who were undergoing autologous stem cell transplantation with high-dose melphalan.
MATERIALS AND METHODS
METHODS
Peripheral blood mononuclear cells (PBMC) were collected from 108 MM patients prior to melphalan therapy. Clinical data were also collected from these patients following melphalan therapy.
RESULTS
RESULTS
rs4240803 was associated with elevated expression of SLC7A5 mRNA, higher ex vivo sensitivity to melphalan in PBMCs, and positive 90-day response in these patients (p=0.047, 0.10, 0.049, respectively).
CONCLUSION
CONCLUSIONS
rs4240803 impacted the expression of SLC7A5, thus contributing to the clinical response of MM patients to melphalan therapy.
Identifiants
pubmed: 30591441
pii: 39/1/67
doi: 10.21873/anticanres.13080
doi:
Substances chimiques
Large Neutral Amino Acid-Transporter 1
0
Melphalan
Q41OR9510P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-72Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.