Loss of ATM gene, del(11q22.3)
The protein kinase ATM (Ataxia-Telangiectasia Mutated) gene located in 11q22.3 is frequently deleted in cases of CLL. The ATM gene is an important checkpoint gene involved in cell damage management. Its function is to assess the level of DNA damage that the cell has received and attempt to repair the DNA by phosphorylating key substrates that are involved in DNA repair. Recently, the ATM-P53 interaction in CLL has been shown to have an important impact on cancer proliferation. The deletion of ATM removes the activation of the P53 protein, despite being present, so damaged cells are allowed to proliferate.
Deletions of ATM and TP53 are the most serious rearrangements involved in CLL and detection of these deletions provides very important treatment information. Deletion of 11q22.3, and therefore ATM, is associated to a poor prognosis.
References
- Stankovic et al., Blood 2004;103(1):291-300
- Khanna et al., Nature Genetics 1998;20(4):398-400
- Zenz T et al (2010) Nature Rev Cancer.10:37-50.
