Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets

Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a pa...

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Published inScientific reports Vol. 7; no. 1; p. 10188
Main Authors Mine, Sohtaro, Hishima, Tsunekazu, Suganuma, Akihiko, Fukumoto, Hitomi, Sato, Yuko, Kataoka, Michiyo, Sekizuka, Tsuyoshi, Kuroda, Makoto, Suzuki, Tadaki, Hasegawa, Hideki, Fukayama, Masashi, Katano, Harutaka
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 31.08.2017
Nature Publishing Group
Subjects
13
13/106
45/77
631/326/596/1553
692/308/1426
692/4028/67/1990/291/1621/1915
692/420/755
82
82/51
82/80
96/31
96/95
Acquired immune deficiency syndrome
Acquired Immunodeficiency Syndrome - complications
AIDS
Antibodies, Monoclonal, Humanized
Apoptosis
c-Myc protein
CD20 antigen
CD38 antigen
Cell culture
Cell Culture Techniques - methods
Cell death
Cell differentiation
Cell Line, Tumor
Cell survival
Culture Media - chemistry
Cytokines
Epstein-Barr virus
Genomes
Heavy chains
Humanities and Social Sciences
Humans
Immunoglobulins
Immunophenotyping
Interleukin 6
Interleukin 6 receptors
Interleukin-6 - pharmacology
Lymphoma
Male
Middle Aged
miRNA
multidisciplinary
Myc protein
Plasmablastic Lymphoma - etiology
Plasmablastic Lymphoma - immunology
Plasmablastic Lymphoma - pathology
Science
Science (multidisciplinary)
Signal transduction
Starvation
Supplements
TOR protein
Transcription
Translocation
Online AccessGet full text

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Abstract Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(−) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.
AbstractList Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(−) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.
Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(-) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.
Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(-) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(-) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.
ArticleNumber 10188
Author Sato, Yuko
Kuroda, Makoto
Suzuki, Tadaki
Fukayama, Masashi
Mine, Sohtaro
Hishima, Tsunekazu
Suganuma, Akihiko
Kataoka, Michiyo
Fukumoto, Hitomi
Katano, Harutaka
Sekizuka, Tsuyoshi
Hasegawa, Hideki
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Snippet Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in...
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SubjectTerms 13
13/106
45/77
631/326/596/1553
692/308/1426
692/4028/67/1990/291/1621/1915
692/420/755
82
82/51
82/80
96/31
96/95
Acquired immune deficiency syndrome
Acquired Immunodeficiency Syndrome - complications
AIDS
Antibodies, Monoclonal, Humanized
Apoptosis
c-Myc protein
CD20 antigen
CD38 antigen
Cell culture
Cell Culture Techniques - methods
Cell death
Cell differentiation
Cell Line, Tumor
Cell survival
Culture Media - chemistry
Cytokines
Epstein-Barr virus
Genomes
Heavy chains
Humanities and Social Sciences
Humans
Immunoglobulins
Immunophenotyping
Interleukin 6
Interleukin 6 receptors
Interleukin-6 - pharmacology
Lymphoma
Male
Middle Aged
miRNA
multidisciplinary
Myc protein
Plasmablastic Lymphoma - etiology
Plasmablastic Lymphoma - immunology
Plasmablastic Lymphoma - pathology
Science
Science (multidisciplinary)
Signal transduction
Starvation
Supplements
TOR protein
Transcription
Translocation
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Title Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets
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Volume 7
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