Abstract |
To obtain further insights into the biological differences of anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK+ ALCL) and classical Hodgkin lymphoma (HL), we screened microbial culture filtrates to search for compounds that would exert a significantly greater effect on the viability of ALK+ ALCL cell lines compared to HL cell lines and identified Brefeldin A (BFA) as a suitable candidate. BFA inhibited phosphorylation of ALK and its downstream molecule, signal transducer and activator of transcription 3 (STAT3), one of the central pathways for the survival of ALK+ ALCL cells. In HL cell lines BFA did not affect CD30 expression or constitutive nuclear factor (NF)-κB activity, both of which are critical for HL cell survival. BFA induced disruption of the Golgi apparatus in ALK+ ALCL cell lines, which was accompanied by a decrease in active ADP-ribosylation factor 1 (ARF1), whereas BFA had no significant effect on these parameters in HL cell lines. These results add extra insights into the biological distinction between ALK+ ALCL and HL cells and highlight the Golgi apparatus as a target for the treatment of ALK+ ALCL.
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Authors | Takashi Toda, Mariko Watanabe, Junji Kawato, Marshall E Kadin, Masaaki Higashihara, Takao Kunisada, Kazuo Umezawa, Ryouichi Horie |
Journal | British journal of haematology
(Br J Haematol)
Vol. 170
Issue 6
Pg. 837-46
(Sep 2015)
ISSN: 1365-2141 [Electronic] England |
PMID | 26105086
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 John Wiley & Sons Ltd. |
Chemical References |
- Ki-1 Antigen
- NF-kappa B
- STAT3 Transcription Factor
- Brefeldin A
- ALK protein, human
- Anaplastic Lymphoma Kinase
- Receptor Protein-Tyrosine Kinases
- ADP-Ribosylation Factor 1
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Topics |
- ADP-Ribosylation Factor 1
(antagonists & inhibitors)
- Anaplastic Lymphoma Kinase
- Brefeldin A
(pharmacology)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Drug Resistance, Neoplasm
- Gene Expression
- Golgi Apparatus
(drug effects)
- Hodgkin Disease
(genetics, metabolism)
- Humans
- Ki-1 Antigen
(genetics, metabolism)
- Lymphoma, Large-Cell, Anaplastic
(genetics, metabolism)
- NF-kappa B
(metabolism)
- Phosphorylation
(drug effects)
- Receptor Protein-Tyrosine Kinases
(genetics, metabolism)
- STAT3 Transcription Factor
(antagonists & inhibitors)
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