Establishment and comprehensive analysis of a new human transformed follicular lymphoma B cell line, Tat-1.
A spontaneously EBV transformed follicular lymphoma (FL) cell line, Tat-1, was established from the lymph node biopsy specimen of a patient with B cell FL, grade 1 in transformation to high grade disease. Tat-1 cells expressed lymphoid markers and developed tumor masses in immunodeficient mice. Bcl-2, Bcl-X(L), Bax and p53 protein expression was revealed by Western blotting. Flow cytometric analysis confirmed P-gp expression. Cytogenetically, the Tat-1 cell line showed identical chromosomal alterations to that of the initial biopsy specimen, among which the most notable were the t(14;18) typical of FL and additional abnormalities involving chromosomes 1, 8 and 13. Multicolor FISH analysis delineated all abnormalities, including a t(1p;8q), a der(8)(8q24::14q32::18q21) and a der(13)(13q32::8q24::14q32::18q21). Further FISH investigations using a locus-specific probe cocktail containing c-myc, IgH and bcl-2 revealed fusion of these three loci on the derivatives 8 and 13, in addition to the derivative 14 IgH/bcl-2 fusion and an extra copy of c-myc on derivative chromosome 1. These results demonstrate an additional example of the deregulation of bcl-2 and c-myc expression through recombination with a single IgH enhancer region. The unusual molecular features of the Tat-1 cell line render it a unique tool for studies focused on cytogenetic alterations, expression of multidrug resistance phenotype and expression of anti-apoptotic proteins in FL.
Denyssevych
T
T
Department of Advanced Therapeutics, Vancouver Cancer Centre, British Columbia Cancer Agency, and the University of British Columbia, Vancouver, BC, Canada.
Lestou
V S
VS
Knesevich
S
S
Robichaud
M
M
Salski
C
C
Tan
R
R
Gascoyne
R D
RD
Horsman
D E
DE
Mayer
L D
LD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology / Q000821:virology; D002472:Cell Transformation, Viral; D002869:Chromosome Aberrations; D020223:Chromosome Painting; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D004317:Doxorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000473:pathology*; D017809:Fatal Outcome; D005260:Female; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007621:Karyotyping; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology* / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D014178:Translocation, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000648:ultrastructure; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; D016159:Tumor Suppressor Protein p53; C064655:V(D)J recombination activating protein 2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D004317:Doxorubicin