Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic leukaemia: Evidence for a pathogenic role of NPAT, CUL5 and PPP2R1B

作者：Kalla Claudia^*; Scheuermann Markus O; Kube Ina; Schlotter Magdalena; Mertens Daniel; Doehner Hartmut; Stilgenbauer Stephan; Lichter Peter

来源：European Journal of Cancer, 2007, 43(8): 1328-1335.

DOI：10.1016/j.ejca.2007.02.005

• B-cell chronic lymphocytic
• leukaemia
• 11q22-q23
• NPAT
• CUL5
• PPP2R1B
• PP2A
• cell cycle
• apoptosis

Deletion of 11q22-q23 is associated with an aggressive course of B-cell chronic lymphocytic leukaemia (B-CLL). Since only in a subset of these cases biallelic inactivation of ATM was observed, we sought to identify other disease-associated genes within 11q22-q23 by analysing NFAT (cell-cycle regulation), CUL5 (ubiquitin-dependent apoptosis regulation) and PPP2R1B (component of the cell-cycle and apoptosis regulating PP2A) for point mutations and their expression in B-CLL by single-strand conformation polymorphism/sequence analysis of the transcripts and real-time polymerase chain reaction. Though none of the genes were affected by deleterious mutations, we observed a significant down-regulation of NPAT in B-CLL versus CD19+ B cells and of CUL5 in 11q deletion versus non-deletion B-CLL samples and measured reduced PPP2R1B transcript levels in a subset of B-CLL cases. Alternative splicing of PPP2R1B transcripts (skipping of exons 2/3, 3, 9) was associated with a reduced activity of protein phosphatase 2A. Together, these results implicate deregulation of the cell-cycle and apoptosis regulators NPAT, CUL5 and PPP2R1B and a role for these genes in the pathogenesis of B-CLL.

• 出版日期2007-5