ArticleLeukemia2012
Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2016Trial
- Heterogeneity of B cell lymphopoiesis in patients with premalignant and active myeloma.JCI insight · 2023Article
- In vitro and ex vivo anti-myeloma effects of nanocomposite AsScientific reports · 2022Article
- Review
- Hedgehog Signaling and Truncated GLI1 in Cancer.Cells · 2020Review
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- A vicious cycle between acid sensing and survival signaling in myeloma cells: acid-induced epigenetic alteration.Oncotarget · 2016Article
- Cancer stem cells: a potential target for cancer therapy.Cellular and molecular life sciences : CMLS · 2015Review
- Dynamic balance of multiple myeloma clonogenic side population cell percentages controlled by environmental conditions.International journal of cancer · 2015Article
- High throughput quantitative reverse transcription PCR assays revealing over-expression of cancer testis antigen genes in multiple myeloma stem cell-like side population cells.British journal of haematology · 2014Article
- Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention.Leukemia · 2014Review
- Targeted therapy for HM1.24 (CD317) on multiple myeloma cells.BioMed research international · 2014Review
- Hypoxia reduces CD138 expression and induces an immature and stem cell-like transcriptional program in myeloma cells.International journal of oncology · 2013Article
- Tumor necrosis factor α-induced hypoxia-inducible factor 1α-β-catenin axis regulates major histocompatibility complex class I gene activation through chromatin remodeling.Molecular and cellular biology · 2013Article
- Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1.American journal of hematology · 2013Article
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Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells have been proposed to be responsible for tumorigenesis and recurrence in various neoplastic diseases, including multiple myeloma (MM). We have previously reported that MM cells specifically express HLA class I at high levels and that single-chain Fv diabody against this molecule markedly induces MM cell death. Here we investigated the effect of a new diabody (C3B3) on cancer stem cell-like side population (SP) cells. SP fraction of MM cells highly expressed ABCG2 and exhibited resistance to chemotherapeutic agents; however, C3B3 induced cytotoxicity in both SP cells and main population (MP) cells to a similar extent. Moreover, C3B3 suppressed colony formation and tumorigenesis of SP cells in vitro and in vivo. Crosslinking of HLA class I by C3B3 mediated disruption of lipid rafts and actin aggregation, which led to inhibition of gene expression of β-catenin and pluripotency-associated transcription factors such as Sox2, Oct3/4 and Nanog. Conversely, knockdown of Sox2 and Oct3/4 mRNA reduced the proportion of SP cells, suggesting that these factors are essential in maintenance of SP fraction in MM cells. Thus, our findings reveal that immunotherapeutic approach by engineered antibodies can overcome drug resistance, and provide a new basis for development of cancer stem cell-targeted therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.