ORIGINAL ARTICLE

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 and A van den Berg¹

¹ Department of Pathology and Laboratory Medicine, Universal Medical Centre Groningen and University of Groningen, 9700 RB Groningen, The Netherlands
² Department of Pathology, University of Malaya, 50603 Kuala Lumpur, Malaysia
³ Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, 84132 USA
⁴ Department of Paediatric Oncology, Universal Medical Centre Groningen and University of Groningen

Correspondence to:
Correspondence to:
Dr A van den Berg
Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands; a.van.den.berg{at}path.azg.nl

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-X_L, 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-X_L in Karpas299 and in four other ALCL cell lines. To expand on these initial observations, primary tissue samples were analysed for Mcl-1, Bcl-X_L, and Bcl-2 by immunohistochemistry. All 23 ALK+ and nine ALK– ALCL cases were positive for Mcl-1. Bcl-2 and Bcl-X_L 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-X_L 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.

Abbreviations: ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; ß2m, ß2 microglobulin; Ct, threshold cycle; RT-PCR, reverse transcription polymerase chain reaction; SAGE, serial analysis of gene expression

Keywords: anaplastic large cell lymphoma; ALK; Bcl-2; Bcl-X L; Mcl-1

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• Amin, H. M., Lai, R. (2007). Pathobiology of ALK+ anaplastic large-cell lymphoma. Blood 110: 2259-2267 [Abstract] [Full Text]