A myeloma cell line established from a patient refractory to thalidomide therapy revealed high-risk cytogenetic abnormalities and produced vascular endothelial growth factor

Hattori, Yutaka; Du, Wei; Yamada, Taketo; Ichikawa, Daiju; Matsunami, Sayuri; Matsushita, Maiko

doi:10.1038/bcj.2013.13

Cited by 8 publications

(9 citation statements)

References 8 publications

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“…T(1;9), (1;18), (6;18) (15;16), and del(5) were also found in plasma cell lines, but on different locuses and very rarely. Other structural abnormalities in UHKT‐944 karyotype appear to have been noted for the first time among plasma cell lines .…”

Section: Discussionmentioning

confidence: 75%

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Characterization of a new human plasma cell leukemia cell line UHKT‐944

Vyhlídalová

Uherková

Pleschnerová

et al. 2015

European J of Haematology

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Section: Discussionmentioning

confidence: 75%

“…The expression of CD138 and CD38 showed plasma cell phenotype. Immunophenotype of the cell line in comparison with other plasma cell‐derived cell lines is summarized in Table . The analysis also revealed the presence of monoclonal cytoplasmic Ig kappa light chain.…”

Section: Resultsmentioning

confidence: 99%

Characterization of a new human plasma cell leukemia cell line UHKT‐944

Vyhlídalová

Uherková

Pleschnerová

et al. 2015

European J of Haematology

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“… 19 The MUM24 cells were obtained from a thalidomide‐resistant MM patient, and the authentication was confirmed by an STR (short tandem repeat)‐PCR (polymerase chain reaction) analysis (Japan National Institute of Biomedical Innovation, Osaka). 20 All of the cell lines were cultured in RPMI1640 medium (Sigma‐Aldrich) containing 10% FBS (fetal bovine serum) (Gibco, Life Technologies) and 1% penicillin–streptomycin (Pen‐Strep, Gibco). Chromosomal abnormalities such as del(17p13.1) and t (4;14) were examined by a FISH (fluorescence in situ hybridization) analysis (LSI Medience, Tokyo).…”

Section: Methodsmentioning

confidence: 99%

GTN057, a komaroviquinone derivative, induced myeloma cells' death in vivo and inhibited c‐MET tyrosine kinase

et al. 2023

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Objective Despite the development of newly developed drugs, most multiple myeloma (MM) patients with high‐risk cytogenetic abnormalities such as t(4;14) or del17p relapse at anin early stage of their clinical course. We previously reported that a natural product,komaroviquinone (KQN), isolated from the perennial semi‐shrub Dracocephalum komarovi , i.e., komaroviquinone (KQN) and its derivative GTN024 induced the apoptosis of MM cells by producing reactive oxygen species (ROS), but both exhibited significant hematological toxicity. Aim of this study is to clarify anti‐tumor activity, safety and pharmacokinetics of GTN057, an optimization compound of KQN in vivo. Methods ICR/SCID xenograft model of KMS11, a t(4;14) translocation‐positive MM cell line, was used for in vivo study. Mice pharmacokinetics of GTN057 and the degradation products were analyzed by LC‐MS/MS. Results Herein, our in vitro experiments revealed that GTN057 is much less toxic to normal hematopoietic cells, induced the apoptosis of both MM cell lines andpatient samples, including those with high‐risk cytogenetic changes. A xenograft model of a high‐risk MM cell line demonstrated that GTN057 significantly delayed the tumor growth with no apparent hematological or systemic toxicities in vivo. The pathological examination of GTN057‐treated tumors in vivoshowed revealed apoptosis of MM cells and anti‐angiogenesis. In addition to the production of ROS, GTN057 inhibited the downstream signaling of c‐MET, a receptor tyrosine kinase a receptor forand hepatocyte growth factor (HGF) receptor. Thus, GTN057 is less toxic and is able tomay be a candidate drug for treating MM patients, via multifunctional mechanisms. We have also extensively studied the pharmacologyical analysis of GTN057. The metabolites of GTN057, (e.g.,such as GTN054), may also have anti‐tumorantitumor activity. Conclusion Natural products or and their derivatives can could be good sources of antineoplastic drugs even for high‐risk cancer.

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“…KMM1, KMS11, KMS20, KMS21, KMS26, KMS27, KMS28, and KMS34 were kindly provided by Dr. Ohtsuki of Kawasaki Medical School (Kurashiki, Japan). MUM24 was established in our laboratory from a thalidomide-resistant patient [ 12 ]. CIR-A24 cells were kindly gifted by Dr. Yutaka Kawakami of Keio University, School of Medicine (Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Characteristics of a Novel Target Antigen against Myeloma Cells for Immunotherapy

et al. 2020

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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 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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A myeloma cell line established from a patient refractory to thalidomide therapy revealed high-risk cytogenetic abnormalities and produced vascular endothelial growth factor

Cited by 8 publications

References 8 publications

Characterization of a new human plasma cell leukemia cell line UHKT‐944

Characterization of a new human plasma cell leukemia cell line UHKT‐944

GTN057, a komaroviquinone derivative, induced myeloma cells' death in vivo and inhibited c‐MET tyrosine kinase

Characteristics of a Novel Target Antigen against Myeloma Cells for Immunotherapy

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