High expression of Mcl-1 in ALK positive and negative anaplastic large cell lymphoma
- R Rust1,
- G Harms1,
- T Blokzijl1,
- M Boot1,
- A Diepstra1,
- J Kluiver1,
- L Visser1,
- S-C Peh2,
- M Lim3,
- W A Kamps4,
- S Poppema1,
- A van den Berg1
- 1Department of Pathology and Laboratory Medicine, Universal Medical Centre Groningen and University of Groningen, 9700 RB Groningen, The Netherlands
- 2Department of Pathology, University of Malaya, 50603 Kuala Lumpur, Malaysia
- 3Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, 84132 USA
- 4Department of Paediatric Oncology, Universal Medical Centre Groningen and University of Groningen
- Correspondence to: Dr A van den Berg Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands; a.van.den.bergpath.azg.nl
- Accepted 13 September 2004
Abstract
Aim: To gain more insight into the genes involved in the aetiology and pathogenesis of anaplastic large cell lymphoma (ALCL).
Methods: Serial analysis of gene expression (SAGE) was undertaken on the CD4+ALK+ (anaplastic lymphoma kinase positive) ALCL derived cell line Karpas299 and as comparison on CD4+ T cells. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed on five ALCL derived cell lines and 32 tissue samples to confirm the SAGE data.
Results: High expression of Mcl-1 was seen in the Karpas299 cell line, whereas the two other antiapoptotic Bcl-2 family members, Bcl-2 and Bcl-XL, were not detected in the SAGE library. Quantitative RT-PCR confirmed the high expression of Mcl-1 mRNA and low expression of Bcl-2 and Bcl-XL in Karpas299 and in four other ALCL cell lines. To expand on these initial observations, primary tissue samples were analysed for Mcl-1, Bcl-XL, and Bcl-2 by immunohistochemistry. All 23 ALK+ and nine ALK− ALCL cases were positive for Mcl-1. Bcl-2 and Bcl-XL were expressed infrequently in ALK+ ALCL cases, but were present in a higher proportion of ALK− ALCL cases.
Conclusion: The consistent high expression of Mcl-1 in ALK+ and ALK− ALCL suggests that Mcl-1 is the main antiapoptotic protein in this disease. The high frequency of Mcl-1, Bcl-2, and Bcl-XL positive ALCL cases in the ALK− group compared with the ALK+ group indicates that ALK induced STAT3 activation is not the main regulatory pathway in ALCL.
- ALCL, anaplastic large cell lymphoma
- ALK, anaplastic lymphoma kinase
- β2m, β2 microglobulin
- Ct, threshold cycle
- RT-PCR, reverse transcription polymerase chain reaction
- SAGE, serial analysis of gene expression
