Epigenetic regulation of CD20 protein expression in a novel B-cell lymphoma cell line, RRBL1, established from a patient treated repeatedly with rituximab-containing chemotherapy

Akihiro Tomita, Junji Hiraga, Hitoshi Kiyoi, Manabu Ninomiya, Takumi Sugimoto, Masafumi Ito, Tomohiro Kinoshita, Tomoki Naoe

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Rituximab is a chimeric monoclonal antibody to the surface antigen CD20 and has provided better outcomes against CD20+ B-cell lymphomas than chemotherapy with conventional antitumor drugs alone. Treatment with rituximab poses a considerable problem, however, because of CD20- tumor transformation and subsequent disease progression. We have established a CD20- lymphoma cell line, RRBL1, from a diffuse large B-cell lymphoma with CD20- transformation from CD20+ follicular lymphoma after treatment with rituximab. RRBL1 was CD10+, CD19+, and CD20- by flow cytometry. CD20 expression was not detected by immunohistochemistry. Immunoblotting with whole RRBL1 cell lysate showed a very faint CD20 band only with longer exposures. The level of CD20 messenger RNA (mRNA) expression detected by quantitative reverse transcriptase-polymerase chain reaction analysis was almost 100 times lower than that in CD20+ lymphoma cells. When we treated RRBL1 cells with trichostatin A, an epigenetic drug that modulates histone-acetylation status, we detected dramatically increased CD20 mRNA and protein expression, suggesting that epigenetic mechanisms may explain the CD20- phenotype in RRBL1 cells. Thus, RRBL1 may be useful not only for analyses of mechanisms for the absence of CD20 expression in vitro but also for exploration of therapies against CD20 - B-cell malignancies in vivo.

Original languageEnglish
Pages (from-to)49-57
Number of pages9
JournalInternational Journal of Hematology
Volume86
Issue number1
DOIs
Publication statusPublished - 01-07-2007
Externally publishedYes

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B-Cell Lymphoma
Epigenomics
Drug Therapy
Cell Line
Lymphoma
trichostatin A
Proteins
Messenger RNA
Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
Surface Antigens
Acetylation
Reverse Transcriptase Polymerase Chain Reaction
Immunoblotting
Antineoplastic Agents
Histones
Disease Progression
Neoplasms
Flow Cytometry
B-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Tomita, Akihiro ; Hiraga, Junji ; Kiyoi, Hitoshi ; Ninomiya, Manabu ; Sugimoto, Takumi ; Ito, Masafumi ; Kinoshita, Tomohiro ; Naoe, Tomoki. / Epigenetic regulation of CD20 protein expression in a novel B-cell lymphoma cell line, RRBL1, established from a patient treated repeatedly with rituximab-containing chemotherapy. In: International Journal of Hematology. 2007 ; Vol. 86, No. 1. pp. 49-57.
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abstract = "Rituximab is a chimeric monoclonal antibody to the surface antigen CD20 and has provided better outcomes against CD20+ B-cell lymphomas than chemotherapy with conventional antitumor drugs alone. Treatment with rituximab poses a considerable problem, however, because of CD20- tumor transformation and subsequent disease progression. We have established a CD20- lymphoma cell line, RRBL1, from a diffuse large B-cell lymphoma with CD20- transformation from CD20+ follicular lymphoma after treatment with rituximab. RRBL1 was CD10+, CD19+, and CD20- by flow cytometry. CD20 expression was not detected by immunohistochemistry. Immunoblotting with whole RRBL1 cell lysate showed a very faint CD20 band only with longer exposures. The level of CD20 messenger RNA (mRNA) expression detected by quantitative reverse transcriptase-polymerase chain reaction analysis was almost 100 times lower than that in CD20+ lymphoma cells. When we treated RRBL1 cells with trichostatin A, an epigenetic drug that modulates histone-acetylation status, we detected dramatically increased CD20 mRNA and protein expression, suggesting that epigenetic mechanisms may explain the CD20- phenotype in RRBL1 cells. Thus, RRBL1 may be useful not only for analyses of mechanisms for the absence of CD20 expression in vitro but also for exploration of therapies against CD20 - B-cell malignancies in vivo.",
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Epigenetic regulation of CD20 protein expression in a novel B-cell lymphoma cell line, RRBL1, established from a patient treated repeatedly with rituximab-containing chemotherapy. / Tomita, Akihiro; Hiraga, Junji; Kiyoi, Hitoshi; Ninomiya, Manabu; Sugimoto, Takumi; Ito, Masafumi; Kinoshita, Tomohiro; Naoe, Tomoki.

In: International Journal of Hematology, Vol. 86, No. 1, 01.07.2007, p. 49-57.

Research output: Contribution to journalArticle

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AU - Tomita, Akihiro

AU - Hiraga, Junji

AU - Kiyoi, Hitoshi

AU - Ninomiya, Manabu

AU - Sugimoto, Takumi

AU - Ito, Masafumi

AU - Kinoshita, Tomohiro

AU - Naoe, Tomoki

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AB - Rituximab is a chimeric monoclonal antibody to the surface antigen CD20 and has provided better outcomes against CD20+ B-cell lymphomas than chemotherapy with conventional antitumor drugs alone. Treatment with rituximab poses a considerable problem, however, because of CD20- tumor transformation and subsequent disease progression. We have established a CD20- lymphoma cell line, RRBL1, from a diffuse large B-cell lymphoma with CD20- transformation from CD20+ follicular lymphoma after treatment with rituximab. RRBL1 was CD10+, CD19+, and CD20- by flow cytometry. CD20 expression was not detected by immunohistochemistry. Immunoblotting with whole RRBL1 cell lysate showed a very faint CD20 band only with longer exposures. The level of CD20 messenger RNA (mRNA) expression detected by quantitative reverse transcriptase-polymerase chain reaction analysis was almost 100 times lower than that in CD20+ lymphoma cells. When we treated RRBL1 cells with trichostatin A, an epigenetic drug that modulates histone-acetylation status, we detected dramatically increased CD20 mRNA and protein expression, suggesting that epigenetic mechanisms may explain the CD20- phenotype in RRBL1 cells. Thus, RRBL1 may be useful not only for analyses of mechanisms for the absence of CD20 expression in vitro but also for exploration of therapies against CD20 - B-cell malignancies in vivo.

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