In vitro-generated stem cell leukaemia showing altered cell cycle progression with distinct signalling of the tyrosine-phosphorylated rasGAP-associated p62(dok) protein

Ralf Huss, Eva M. Weissinger, Claudia Lange, Petros Gatsios, Günther Eissner, Hans Jochem Kolb, Joachim Diebold, Peter C. Heinrich, Lutz Graeve

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

In an attempt to gain more insight into the events of leukaemic transformation, a cell line overexpressing MHC class II (DR) was generated by transfecting an early CD34-negative haematopoietic progenitor stem cell line with the appropriate constructs. The stable transfection with genes for DR antigens leads to cellular transformation. The DR+ transformed cell clones express a tyrosine-phosphorylated DR heterodimer and show a significantly different morphology. DR+ clones present the morphology of an immature myeloid neoplasia expressing α-naphthylacetate-esterase (ANAE), but neither myeloperoxidase nor CD34. While D064 cells predominately grow adherent as fibroblast-like cells, the DR+ clones display a decrease in adherent growth. Although both cell lines express similar amounts of the interleukin-6 (IL-6) signal transducer gp130, the DR-transfected cells still show activation of STAT factors by IL-6, whereas D064 cells do not. Although the transformed clones present acceleration of cell-cycle transition and growth, the G0/G1 progression inhibitor p27(kip-1) is up-regulated, while the expression of proteins involved in the S/G2 phase transition, such as cyclin B and cdc2 (p34), is suppressed. Instead cyclin D3, one of the G0/G1 progression factors, is up-regulated, as well as tyrosine-phosphorylated p62(dok), suggesting dysregulation of cell cycle-controlling proteins. In addition, DR+ leukaemia-like cells also overexpress-Bcl-2, while bax expression is suppressed, compared with the wild-type (wt) parental haematopoietic stem cell line. Copyright (C) 200 John Wiley and Sons, Ltd.

Original languageEnglish
Pages (from-to)363-372
Number of pages10
JournalJournal of Pathology
Volume192
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Haematopoietic stem cell leukaemia
  • MHC class II
  • p62(dok)

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