Addition of low‐dose decitabine to bortezomib and dexamethasone as second‐line therapy in multiple myeloma

Li, Ning; Liu, Lina; Xiang, Ping; Liu, Liang; Wang, Juan; Wang, Yaomei; Luo, Suxia; Song, Yongping; Fang, Baijun

doi:10.1111/bjh.16686

Cited by 9 publications

(3 citation statements)

References 16 publications

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“…These tumors could benefit from specific inhibitors of E3-ligases [52]. While the addition of low dose of decitabine, a DNA methylation inhibitor, could add to the effect of BTZ in the treatment of refractory multiple myeloma [53], the addition of bortezomib to decitabine did not improve the therapeutic outcome in acute myeloid leukemia patients [54]. Our results indicate that lower DNA methylation of the proteasome genes is often associated with worse survival, therefore we suggest that such combinations should be carefully designed.…”

Section: Discussionmentioning

confidence: 99%

Expression and DNA methylation of 20S proteasome subunits as prognostic and resistance markers in cancer

Al-Abdulla,

Venz,

Al-Ali

et al. 2023

Preprint

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Proteasomes are involved in the maintenance of cellular protein homeostasis and the control of numerous cellular pathways. Single proteasome genes or subunits have been identified as important players in cancer development and progression without considering the proteasome as a multi-subunit protease. We here conduct a comprehensive pan-cancer analysis encompassing transcriptional, epigenetic, mutational landscapes, pathway enrichments, and survival outcomes linked to the 20S proteasome core complex. The impact of proteasome gene expression on patient survival exhibits a cancer-type dependent pattern. Escalated proteasome expression associates with elevated activation of oncogenic pathways, such as DNA repair, MYC- controlled gene networks, MTORC1 signaling, oxidative phosphorylation, as well as metabolic pathways including glycolysis and fatty acid metabolism. Vice versa, potential loss of function variants correlates with improved survival. The TCGA-derived outcomes are further supported by gene expression analysis of THP-1 cells. Our study reframes these subunits as an integrated functional ensemble, rather than separated subunits.Abstract Figure

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Section: Discussionmentioning

confidence: 99%

Expression and DNA methylation of 20S proteasome subunits as prognostic and resistance markers in cancer

Al-Abdulla,

Venz,

Al-Ali

et al. 2023

Preprint

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“…5-aza and DAC have been approved for the treatment of myelodysplastic syndrome without severe side effects [27]. However, few reports exist on their use in myeloma patients [28]. In particular, DAC showed a more potent response compared to 5-aza in inducing both antigen expression and CTL recognition.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of a Novel Target Antigen against Myeloma Cells for Immunotherapy

Matsushita¹,

Saito²,

Yokoe³

et al. 2020

Preprint

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Despite the availability of therapeutic treatments, multiple myeloma is an incurable haematological disorder. In this study, we aimed to clarify the role of CXorf48 as a therapeutic target in multiple myeloma. Based on a previously identified HLA-A*24:02-restiricted epitope from this novel cancer/testis antigen, we characterized the activities of cytotoxic T lymphocytes (CTLs) specific to this antigen against myeloma cells and evaluated the effects of demethylating agents in increasing antigen expression and enhancing the cytotoxic activity of CTLs. CXorf48 expression was examined by RT-PCR using nine myeloma cell lines. Cell lines with low CXorf48 expression were treated by demethylating agents (DMAs), 5-azacytidine (5-aza), and 5-aza-2'-deoxycytidine (DAC) to evaluate gene expression using quantitative RT-PCR. Furthermore, CXorf48-specific CTLs were induced from peripheral blood mononuclear cells of HLA-A*24:02-positive healthy donors to evaluate antigen recognition using ELISpot and 51Cr cytotoxicity assays. CXorf48 was widely expressed in myeloma cells and gene expression was significantly increased by DMAs. Furthermore, CXorf48-specific CTLs recognized DMA-treated myeloma cells. These findings suggest that CXorf48 is a useful target for immunotherapy, such as vaccination, in combination with demethylating agents for the treatment of patients with myeloma.

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“…5-aza and DAC have been approved for the treatment of myelodysplastic syndrome without severe side effects [28]. However, few reports exist on their use in myeloma patients [29]. In particular, DAC showed a more potent response compared to 5-aza in inducing both antigen expression and CTL recognition.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of a Novel Target Antigen against Myeloma Cells for Immunotherapy

et al. 2020

View full text Add to dashboard Cite

Despite the availability of therapeutic treatments, multiple myeloma is an incurable haematological disorder. In this study, we aimed to clarify the role of CXorf48 as a therapeutic target in multiple myeloma. Based on a previously identified HLA-A*24:02-restiricted epitope from this novel cancer/testis antigen, we characterized the activities of cytotoxic T lymphocytes (CTLs) specific to this antigen against myeloma cells and evaluated the effects of demethylating agents in increasing antigen expression and enhancing the cytotoxic activity of CTLs. CXorf48 expression was examined by reverse transcription polymerase chain reaction (RT-PCR) using nine myeloma cell lines. Cell lines with low CXorf48 expression were treated by demethylating agents (DMAs), 5-azacytidine (5-aza), and 5-aza-2'-deoxycytidine (DAC) to evaluate gene expression using quantitative RT-PCR. Furthermore, CXorf48-specific CTLs were induced from peripheral blood mononuclear cells of HLA-A*24:02-positive healthy donors to evaluate antigen recognition using ELISpot and 51Cr cytotoxicity assays. CXorf48 was widely expressed in myeloma cells, and gene expression was significantly increased by DMAs. Furthermore, CXorf48-specific CTLs recognized DMA-treated myeloma cells. These findings suggest that CXorf48 is a useful target for immunotherapy, such as vaccination, in combination with demethylating agents for the treatment of patients with myeloma.

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Addition of low‐dose decitabine to bortezomib and dexamethasone as second‐line therapy in multiple myeloma

Cited by 9 publications

References 16 publications

Expression and DNA methylation of 20S proteasome subunits as prognostic and resistance markers in cancer

Expression and DNA methylation of 20S proteasome subunits as prognostic and resistance markers in cancer

Characteristics of a Novel Target Antigen against Myeloma Cells for Immunotherapy

Characteristics of a Novel Target Antigen against Myeloma Cells for Immunotherapy

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