Characterization of 4 mantle cell lymphoma cell lines.
BACKGROUND
Mantle cell lymphoma (MCL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by t(11;14)(q13;q32) and cyclin D1 overexpression. The pathogenesis of MCL has not been comprehensively studied, which can be attributed in part to the paucity of well-characterized MCL cell lines.


OBJECTIVE
We collected 4 previously developed MCL cell lines and performed extensive characterization, including the susceptibly of these cell lines to transduction by adenovirus vectors. Our aim was to facilitate the establishment of an in vitro model that can be reliably used to study the pathogenesis of MCL.


METHODS
Standard techniques were used to compare the morphologic, immunophenotypic, and cytogenetic features of the 4 cell lines. In addition, Western blotting was used to investigate the presence of several cell cycle- and apoptosis-related proteins. TP53 DNA sequencing was also performed on the cell lines. The adenoviral transduction efficiency was assessed using an adenoviral vector carrying the gene encoding for the green fluorescence protein (Ad-GFP).


RESULTS
All cell lines demonstrated evidence of t(11;14)(q13;q32) and overexpression of cyclin D1. Cyclin D2 was not detectable in all cell lines, whereas cyclin D3 was weakly expressed in JeKo-1 and SP-53. Other abnormalities of the cell cycle G1 phase regulatory pathway were detected, including loss of expression of p53 (JeKo-1) and p16(INK4a) (SP-53 and Granta 519), as well as TP53 mutation (Mino). All cell lines express high levels of cyclin E, c-Myc, Bcl-2, Bax, Bcl-x(L), and Mcl-1. Retinoblastoma protein is hyperphosphorylated in all cell lines. With the exception of Mino, MCL cell lines are highly transducible with adenoviral vectors.


CONCLUSIONS
These cell lines are representative of MCL and can be used as an in vitro model to further explore the pathogenesis of this disease. The susceptibility of these cell lines to gene transfer provides opportunities to evaluate the importance of various oncogenes and tumor suppressor genes that may have an impact on developing effective therapeutic regimens for MCL.
Amin
Hesham M
HM
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
McDonnell
Timothy J
TJ
Medeiros
L Jeffrey
LJ
Rassidakis
Georgios Z
GZ
Leventaki
Vasiliki
V
O'Connor
Sean L
SL
Keating
Michael J
MJ
Lai
Raymond
R
D000256:Adenoviridae / Q000235:genetics; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002472:Cell Transformation, Viral / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D020732:Cytogenetic Analysis / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016130:Immunophenotyping / Q000379:methods; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D009154:Mutation / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D000954:Antigens, Surface; D018797:Cell Cycle Proteins; D008164:Luminescent Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins