Quantitative expression of Ikaros, IRF4, and PSMD10 proteins predicts survival in VRD-treated patients with multiple myeloma.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
08 12 2020
08 12 2020
Historique:
received:
23
06
2020
accepted:
26
10
2020
entrez:
7
12
2020
pubmed:
8
12
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
The search for biomarkers based on the mechanism of drug action has not been thoroughly addressed in the therapeutic approaches to multiple myeloma (MM), mainly because of the difficulty in analyzing proteins obtained from purified plasma cells. Here, we investigated the prognostic impact of the expression of 12 proteins involved in the mechanism of action of bortezomib, lenalidomide, and dexamethasone (VRD), quantified by capillary nanoimmunoassay, in CD138-purified samples from 174 patients with newly diagnosed MM treated according to the PETHEMA/GEM2012 study. A high level of expression of 3 out of 5 proteasome components tested (PSMD1, PSMD4, and PSMD10) negatively influenced survival. The 5 analyzed proteins involved in lenalidomide's mode of action were associated with time to progression (TTP); low levels of cereblon and IRF4 protein and high levels of Ikaros, AGO2, and Aiolos were significantly associated with shorter TTP. Although the glucocorticoid receptor (GCR) level by itself had no significant impact on MM prognosis, a high XPO1 (exportin 1)/GCR ratio was associated with shorter TTP and progression-free survival (PFS). The multivariate Cox model identified high levels of PSMD10 (hazard ratio [HR] TTP, 3.49; P = .036; HR PFS, 5.33; P = .004) and Ikaros (HR TTP, 3.01, P = .014; HR PFS, 2.57; P = .028), and low levels of IRF4 protein expression (HR TTP, 0.33; P = .004; HR PFS, 0.35; P = .004) along with high-risk cytogenetics (HR TTP, 3.13; P < .001; HR PFS, 2.69; P = .002), as independently associated with shorter TTP and PFS. These results highlight the value of assessing proteins related to the mechanism of action of drugs used in MM for predicting treatment outcome.
Identifiants
pubmed: 33284947
pii: S2473-9529(20)32029-2
doi: 10.1182/bloodadvances.2020002711
pmc: PMC7724915
doi:
Substances chimiques
IKZF1 protein, human
0
Interferon Regulatory Factors
0
PSMD10 protein, human
0
Proto-Oncogene Proteins
0
interferon regulatory factor-4
0
Ikaros Transcription Factor
148971-36-2
Bortezomib
69G8BD63PP
Dexamethasone
7S5I7G3JQL
Proteasome Endopeptidase Complex
EC 3.4.25.1
Lenalidomide
F0P408N6V4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6023-6033Informations de copyright
© 2020 by The American Society of Hematology.
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