title: Simian AIDS-related lymphoma growth in severe combined immunodeficiency mice is independent of karyotypic abnormalities or Bcl-6 mutations.
abstract: Simian AIDS-related lymphomas (sARL) of cynomolgus monkeys infected with a simian immunodeficiency virus (SIVsm) were studied in relation to growth in severe combined immunodeficient (SCID) mice, karyotype abnormalities, and DNA sequence of the first noncoding region of the Bcl-6 gene. The tumors were diffuse large B cell lymphomas and expressed a simian homolog to Epstein-Barr virus (HVMF-1) in 12 of 13 primary tumors and corresponding cell lines. A tested cell line was tumorigenic in SCID mice. Tumors in the SCID mice showed cell growth features similar to those in the original lymphoma, suggesting that no subpopulation with growth advantage was selected for in the mice. Spectral karyotype analysis of sARL cell lines showed normal cytogenetic features except for a trisomy of monkey chromosome 2 (corresponding to human chromosomes 7 and 21) in two of five sARL lines, which was not recovered in SCID tumors established from the same cell line. Sequence analysis of a Bcl-6 gene fragment showed sequence variations indicative of population polymorphism(s) in 10 of 13 sARLs, and no evidence of Bcl-6 mutations. Thus Bcl-6 mutations in the first noncoding region are irrelevant for sARL development in cynomolgus monkeys and for tumorigenicity of sARL cell lines. We also demonstrate that no cytogenetic alterations are needed for the development of highly aggressive lymphomas in the SIV-immunosuppressed host.
authors.affiliation: Immunopathology Laboratory, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Castaños-Vélez
authors.forename: Thomas
authors.initials: T
authors.lastname: Heiden
authors.forename: Charlotta
authors.initials: C
authors.lastname: Lindvall
authors.forename: Daniela
authors.initials: D
authors.lastname: Capello
authors.forename: Agneta
authors.initials: A
authors.lastname: Sandlund
authors.forename: Stefan
authors.initials: S
authors.lastname: Imreh
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blennow
authors.forename: Leif C
authors.initials: LC
authors.lastname: Andersson
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Peter
authors.initials: P
authors.lastname: Biberfeld
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D002875:Chromosomes / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D007963:Leukocytes, Mononuclear / Q000473:pathology; D016483:Lymphoma, AIDS-Related / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008252:Macaca fascicularis; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications*; D014157:Transcription Factors / Q000235:genetics*; D014314:Trisomy
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors