Down-regulation of CD9 expression and its correlation to tumor progression in B lymphomas

Sun Ok Yoon, Xin Zhang, Arnold S. Freedman, David Zahrieh, Izidore Lossos, Li Li, Yong Sung Choi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Histological transformation, a pivotal event in the natural history of cancers including lymphomas, is typically associated with more aggressive clinical behavior. L3055, a B lymphoma cell line of germinal center (GC) origin, is dependent on follicular dendritic cells (FDCs) for survival and proliferation, similar to GC-B cells. However, L3055 cells become less FDC-dependent after prolonged culture, which is analogous to transformation in vivo. Comparison of two L3055 subclones (i.e. , the FDC-dependent indolent clone 12 and the FDC-independent aggressive clone 33) by DNA microarray revealed that CD9 was the most differentially expressed gene (P = 0.05). L3055-12 expresses high levels of CD9 while L3055-33 does not. Reduced levels or loss of CD9 expression is also observed in other CD9-positive B lymphoma cell lines. The resultant CD9-negative cells grow faster than CD9-positive cells due to their greater resistance to apoptosis. Furthermore, CD9-negative cells are less dependent on FDCs for their survival and growth compared with CD9-positive cells. CD9 down-regulation in B lymphomas appears to be controlled epigenetically, mainly through histone modifications. These findings imply that CD9 is inversely correlated with B lymphoma progression, and CD9 inactivation may play an important role in B lymphoma transformation.

Original languageEnglish
Pages (from-to)377-386
Number of pages10
JournalAmerican Journal of Pathology
Volume177
Issue number1
DOIs
StatePublished - Jul 1 2010

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Follicular Dendritic Cells
Lymphoma
Down-Regulation
Neoplasms
Germinal Center
Cell Survival
Histone Code
Clone Cells
Cell Line
Oligonucleotide Array Sequence Analysis
B-Lymphocytes
Cell Proliferation
Apoptosis
Growth
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Down-regulation of CD9 expression and its correlation to tumor progression in B lymphomas. / Yoon, Sun Ok; Zhang, Xin; Freedman, Arnold S.; Zahrieh, David; Lossos, Izidore; Li, Li; Choi, Yong Sung.

In: American Journal of Pathology, Vol. 177, No. 1, 01.07.2010, p. 377-386.

Research output: Contribution to journalArticle

Yoon, Sun Ok ; Zhang, Xin ; Freedman, Arnold S. ; Zahrieh, David ; Lossos, Izidore ; Li, Li ; Choi, Yong Sung. / Down-regulation of CD9 expression and its correlation to tumor progression in B lymphomas. In: American Journal of Pathology. 2010 ; Vol. 177, No. 1. pp. 377-386.
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