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High expression of Mcl-1 in ALK positive and negative anaplastic large cell lymphoma
  1. R Rust1,
  2. G Harms1,
  3. T Blokzijl1,
  4. M Boot1,
  5. A Diepstra1,
  6. J Kluiver1,
  7. L Visser1,
  8. S-C Peh2,
  9. M Lim3,
  10. W A Kamps4,
  11. S Poppema1,
  12. A van den Berg1
  1. 1Department of Pathology and Laboratory Medicine, Universal Medical Centre Groningen and University of Groningen, 9700 RB Groningen, The Netherlands
  2. 2Department of Pathology, University of Malaya, 50603 Kuala Lumpur, Malaysia
  3. 3Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, 84132 USA
  4. 4Department of Paediatric Oncology, Universal Medical Centre Groningen and University of Groningen
  1. Correspondence to:
 Dr A van den Berg
 Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands;


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
  • anaplastic large cell lymphoma
  • ALK
  • Bcl-2
  • Bcl-X L
  • Mcl-1

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