ATM Deletion LPH011 - Detail

The protein kinase ATM (Ataxia-Telangiectasia Mutated) gene located in 11q22.3 is frequently deleted in cases of B-CLL. The ATM gene is an important checkpoint gene involved in cell damage management and its function is to assess the level of DNA damage that the cell has received and to attempt repair by phosphorylating key substrates involved in DNA repair. Recently, the ATM/p53 interaction in B-CLL has been shown to have an important impact on the proliferation or otherwise of the cancer¹ It has been shown that ATM concurrently enhances the phosphorylation of p53² should the damage to the cell be so great that it should be destroyed by apoptosis (which is mediated by p53). Deletion of ATM therefore removes this checkpoint activity and hence activation of P53 gene. Thus, there is no attempt at repairing damaged cells and no apoptosis of these cells despite the p53 protein being present. In the absence of ATM, damaged cells are allowed to proliferate. Deletions of ATM and P53 are the most serious rearrangements involved in CLL and detection of deletions of these genes provides very important information as to the therapy choices for such patients especially since deletions of 11q22.3 and therefore ATM provide a poor prognosis.

Reference:/Bibliographie/Literatur/Bibliografia

1. Stankovic et al., 2004 Blood 103(1):291-300
2. Khanna et al.,1998. Nature Genetics. 20(4):398-400