Research

Molecular and cytological features of the mouse B-cell lymphoma line iMyc^Eμ-1

Seong Su Han¹ , Arthur L Shaffer² , Liangping Peng¹ , Seung Tae Chung¹ , Jae Hwan Lim^3,6 , Sungho Maeng⁴ , Joong Su Kim^1,6 , Nicole McNeil⁵ , Thomas Ried⁵ , Louis M Staudt² and Siegfried Janz¹

¹  Laboratory of Genetics, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD, USA

²  Metabolism Branch, CCR, NCI, NIH, Bethesda, MD, USA

³  Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, MD, USA

⁴  Laboratory of Cellular Carcinogenesis and Tumor Promotion, CCR, NCI, NIH, Bethesda, MD, USA

⁵  Genetics Branch, CCR, NCI, NIH, Bethesda, MD, USA

⁶  Korea Research Institutes of Bioscience and Biotechnology, Daejeon (J. S. K.) and Department of Biological Sciences, Andong National University, Andong, South Korea (J. H. L.)

author email corresponding author email

Molecular Cancer 2005, 4:40doi:10.1186/1476-4598-4-40

Published:	9 November 2005

Abstract

Background

Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMyc^Eμ 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 iMyc^Eμ mice that carry a His₆-tagged mouse Myc cDNA, Myc^His, just 5' of the immunoglobulin heavy-chain enhancer, Eμ, are prone to B cell and plasma cell tumors. The predominant tumor (~50%) that arose in the iMyc^Eμ 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 iMyc^Eμ-1, for the in-depth evaluation of LBL in vitro.

Methods

The morphological features and the surface marker expression profile of the iMyc^Eμ-1 cells were evaluated using cytological methods and FACS, respectively. The cytogenetic make-up of the iMyc^Eμ-1 cells was assessed by spectral karyotyping (SKY). The expression of the inserted Myc^His gene was determined using RT-PCR and qPCR. Clonotypic immunoglobulin gene arrangements were detected by Southern blotting. The global gene expression program of the iMyc^Eμ-1 cells and the expression of 768 "pathway" genes were determined with the help of the Mouse Lymphochip^© and Superarray^© cDNA micro- and macroarrays, respectively. Array results were verified, in part, by RT-PCR and qPCR.

Results

Consistent with their derivation from LBL, the iMyc^Eμ-1 cells were found to be neoplastic IgM^highIgD^low lymphoblasts that expressed typical B-cell surface markers including CD40, CD54 (ICAM-1), CD80 (B7-1) and CD86 (B7-2). The iMyc^Eμ-1 cells harbored a reciprocal T(9;11) and three non-reciprocal chromosomal translocations, over-expressed Myc^His at the expense of normal Myc, and exhibited gene expression changes on Mouse Lymphochip^© microarrays that were consistent with Myc^His-driven B-cell neoplasia. Upon comparison to normal B cells using eight different Superarray^© cDNA macroarrays, the iMyc^Eμ-1 cells showed the highest number of changes on the NFκB array.

Conclusion

The iMyc^Eμ-1 cells may provide a uniquely useful model system to study the growth and survival requirements of Myc-driven mouse LBL in vitro.