The impact of SAMHD1 expression and mutation status in mantle cell lymphoma: An analysis of the MCL Younger and Elderly trial.
Adult
Age Factors
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Biomarkers, Tumor
/ genetics
Cell Line, Tumor
Cyclophosphamide
/ pharmacology
Cytarabine
/ pharmacology
DNA Mutational Analysis
Disease-Free Survival
Dose-Response Relationship, Drug
Doxorubicin
/ pharmacology
Drug Resistance, Neoplasm
/ drug effects
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Lymphoma, B-Cell
/ drug therapy
Lymphoma, Mantle-Cell
/ drug therapy
Male
Middle Aged
Mutation
Oxaliplatin
/ pharmacology
Prednisone
/ pharmacology
Primary Cell Culture
Rituximab
/ pharmacology
SAM Domain and HD Domain-Containing Protein 1
/ genetics
Tissue Array Analysis
Vidarabine
/ analogs & derivatives
Vincristine
/ pharmacology
B cell lymphoma
SAMHD1
cytarabine
mantle cell lymphoma
resistance
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 01 2021
01 01 2021
Historique:
received:
11
02
2020
revised:
17
05
2020
accepted:
11
06
2020
pubmed:
9
7
2020
medline:
11
6
2021
entrez:
9
7
2020
Statut:
ppublish
Résumé
The sterile alpha motif and histidine-aspartic domain-containing protein 1 (SAMHD1) has been demonstrated to predict the response to high-dose cytarabine consolidation treatment in acute myeloid leukemia patients. Here, we evaluated SAMHD1 as potential biomarker for the response to high-dose cytarabine in mantle cell lymphoma (MCL) patients. We quantified SAMHD1 protein expression and determined the mutation status in patients of the MCL Younger and Elderly trials (n = 189), who had received high-dose cytarabine- or fludarabine-based polychemotherapy. Additionally, we quantified SAMHD1 expression in B cell lymphoma cell lines and exposed them to cytarabine, fludarabine, and clinically relevant combinations. Across both trials investigated, SAMHD1 mutations had a frequency of 7.1% (n = 13) and did not significantly affect the failure-free survival (FFS, P = .47). In patients treated with high-dose cytarabine- or fludarabine-containing regimes, SAMHD1 expression was not significantly associated with FFS or complete remission rate. SAMHD1 expression in B cell lymphoma cell lines, however, inversely correlated with their in vitro response to cytarabine as single agent (R = .65, P = .0065). This correlation could be reversed by combining cytarabine with other chemotherapeutics, such as oxaliplatin and vincristine, similar to the treatment regime of the MCL Younger trial. We conclude that this might explain why we did not observe a significant association between SAMHD1 protein expression and the outcome of MCL patients upon cytarabine-based treatment.
Substances chimiques
Biomarkers, Tumor
0
R-CHOP protocol
0
Cytarabine
04079A1RDZ
Oxaliplatin
04ZR38536J
Rituximab
4F4X42SYQ6
Vincristine
5J49Q6B70F
Doxorubicin
80168379AG
Cyclophosphamide
8N3DW7272P
SAM Domain and HD Domain-Containing Protein 1
EC 3.1.5.-
SAMHD1 protein, human
EC 3.1.5.-
Vidarabine
FA2DM6879K
fludarabine
P2K93U8740
Prednisone
VB0R961HZT
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
150-160Informations de copyright
© 2020 UICC.
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