High expression of Mcl-1 in ALK positive and negative anaplastic large cell lymphoma

R Rust, G Harms, T Blokzijl, M Boot, A Diepstra, J Kluiver, L Visser, SC Peh, M Lim, WA Kamps, S Poppema, Anke van den Berg

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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-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 ALK2 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 ALK2 ALCL cases.

Conclusion: The consistent high expression of Mcl-1 in ALK+ and ALK2 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 ALK2 group compared with the ALK+ group indicates that ALK induced STAT3 activation is not the main regulatory pathway in ALCL.

Original languageEnglish
Pages (from-to)520-524
Number of pages5
JournalJournal of Clinical Pathology
Volume58
Issue number5
DOIs
Publication statusPublished - May-2005

Keywords

  • BCL-2 FAMILY PROTEINS
  • DIFFERENTIAL EXPRESSION
  • HEMATOPOIETIC-CELLS
  • GENE-EXPRESSION
  • KI-1 LYMPHOMA
  • MYELOMA CELLS
  • UP-REGULATION
  • CDNA ARRAYS
  • APOPTOSIS
  • STAT3

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