title: Molecular and cytological features of the mouse B-cell lymphoma line iMycEmu-1.
abstract: BACKGROUND
  Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMycEmu mice may provide a model system for the study of the mechanism by which human MYC facilitates the initiation and progression of B cell and plasma cell neoplasms in human beings. We have recently shown that gene-targeted iMycEmu mice that carry a His6-tagged mouse Myc cDNA, MycHis, just 5' of the immunoglobulin heavy-chain enhancer, Emu, are prone to B cell and plasma cell tumors. The predominant tumor (approximately 50%) that arose in the iMycEmu mice on the mixed genetic background of segregating C57BL/6 and 129/SvJ alleles was LBL. The purpose of this study was to establish and characterize a cell line, designated iMycEmu-1, for the in-depth evaluation of LBL in vitro.
  
  
  METHODS
  The morphological features and the surface marker expression profile of the iMycEmu-1 cells were evaluated using cytological methods and FACS, respectively. The cytogenetic make-up of the iMycEmu-1 cells was assessed by spectral karyotyping (SKY). The expression of the inserted MycHis gene was determined using RT-PCR and qPCR. Clonotypic immunoglobulin gene arrangements were detected by Southern blotting. The global gene expression program of the iMycEmu-1 cells and the expression of 768 "pathway" genes were determined with the help of the Mouse Lymphochip(c) and Superarray(c) cDNA micro- and macroarrays, respectively. Array results were verified, in part, by RT-PCR and qPCR.
  
  
  RESULTS
  Consistent with their derivation from LBL, the iMycEmu-1 cells were found to be neoplastic IgMhighIgDlow lymphoblasts that expressed typical B-cell surface markers including CD40, CD54 (ICAM-1), CD80 (B7-1) and CD86 (B7-2). The iMycEmu-1 cells harbored a reciprocal T(9;11) and three non-reciprocal chromosomal translocations, over-expressed MycHis at the expense of normal Myc, and exhibited gene expression changes on Mouse Lymphochip microarrays that were consistent with MycHis-driven B-cell neoplasia. Upon comparison to normal B cells using eight different Superarray cDNA macroarrays, the iMycEmu-1 cells showed the highest number of changes on the NFkappaB array.
  
  
  CONCLUSIONS
  The iMycEmu-1 cells may provide a uniquely useful model system to study the growth and survival requirements of Myc-driven mouse LBL in vitro.
authors.affiliation: Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA. hanse@mail.nih.gov
authors.forename: Seong Su
authors.initials: SS
authors.lastname: Han
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Shaffer
authors.forename: Liangping
authors.initials: L
authors.lastname: Peng
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Chung
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Lim
authors.forename: Sungho
authors.initials: S
authors.lastname: Maeng
authors.forename: Joong Su
authors.initials: JS
authors.lastname: Kim
authors.forename: Nicole
authors.initials: N
authors.lastname: McNeil
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Siegfried
authors.initials: S
authors.lastname: Janz
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D007621:Karyotyping; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc