Abstract | OBJECTIVE: METHODS: 132 patients with MM were divided into responders (78 cases) and nonresponders (54 cases) according to the efficacy evaluated after four cycles of GC-dependent regimen. 66 patients with iron-deficiency anemia were served as controls. Preparation of mononuclear bone marrow cells (MBMCs) was purified by Ficoll- Hypaque gradient centrifugation. The mRNA expression of GR α, β, γ, P, SRp30, SRp40, HSP90, NF-κB and AP-1 were detected by real time RT-PCR. TRIAL REGISTRATION: CHiCTR-RCH-12002872. RESULTS: The expression of four GR isoforms exhibited the following trend in MM patients and controls: GRα> GR-P>GRγ>GRβ. GRα and HSP90 expression in responders was significantly higher than that of the nonresponders (P<0.050). HSP90/GRα expression in MM patients exhibited significantly higher than that in controls (P<0.001). SRp30c and SRp40 mRNA expression both showed significant positive correlation with GRα transcript (P<0.001). Compared with controls, NF-kB and AP -1 expression in MM patients was higher. NF-kB and AP-1 expression of nonresponders were significantly higher than that of responders. The difference was not obvious statistically (P>0.050). CONCLUSION: Our findings raise the possibility that low expression of GRα and HSP90 plays important roles in nonresponders. Lack of HSP90 might affect GR structure and further take part in nonresponse. SRp30c and SRp40 mRNA expression both showed significant positive correlation with GRα. That might become new targets for treatment of nonresponders in MM patients, although further studies are needed for clarification.
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Authors | Yanchun Guan, Yang Si, Wei Cai, Liangliang Ma, Meiyun Fang |
Journal | Annals of clinical and laboratory science
(Ann Clin Lab Sci)
Vol. 51
Issue 6
Pg. 805-817
(Nov 2021)
ISSN: 1550-8080 [Electronic] United States |
PMID | 34921034
(Publication Type: Journal Article)
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Copyright | © 2021 by the Association of Clinical Scientists, Inc. |
Chemical References |
- Antineoplastic Agents
- Biomarkers, Pharmacological
- Glucocorticoids
- HSP90 Heat-Shock Proteins
- NF-kappa B
- Protein Isoforms
- RNA, Messenger
- Receptors, Glucocorticoid
- Transcription Factor AP-1
- Serine-Arginine Splicing Factors
- Thalidomide
- Bortezomib
- Dexamethasone
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Topics |
- Antineoplastic Agents
(pharmacology)
- Biomarkers, Pharmacological
(analysis)
- Bortezomib
(pharmacology)
- Dexamethasone
(pharmacology)
- Drug Monitoring
(methods)
- Female
- Gene Expression Profiling
(methods)
- Gene Expression Regulation
(drug effects)
- Glucocorticoids
(pharmacology)
- HSP90 Heat-Shock Proteins
(metabolism)
- Humans
- Male
- Middle Aged
- Multiple Myeloma
(drug therapy, metabolism, pathology)
- NF-kappa B
(metabolism)
- Protein Isoforms
(chemistry, genetics, isolation & purification)
- RNA, Messenger
(genetics)
- Receptors, Glucocorticoid
(chemistry, genetics)
- Serine-Arginine Splicing Factors
(metabolism)
- Thalidomide
(pharmacology)
- Transcription Factor AP-1
(metabolism)
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