title: High expression of Mcl-1 in ALK positive and negative anaplastic large cell lymphoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Universal Medical Centre Groningen and University of Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Rust
authors.forename: G
authors.initials: G
authors.lastname: Harms
authors.forename: T
authors.initials: T
authors.lastname: Blokzijl
authors.forename: M
authors.initials: M
authors.lastname: Boot
authors.forename: A
authors.initials: A
authors.lastname: Diepstra
authors.forename: J
authors.initials: J
authors.lastname: Kluiver
authors.forename: L
authors.initials: L
authors.lastname: Visser
authors.forename: S-C
authors.initials: SC
authors.lastname: Peh
authors.forename: M
authors.initials: M
authors.lastname: Lim
authors.forename: W A
authors.initials: WA
authors.lastname: Kamps
authors.forename: S
authors.initials: S
authors.lastname: Poppema
authors.forename: A
authors.initials: A
authors.lastname: van den Berg
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D017209:Apoptosis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051020:bcl-X Protein; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases