CytoCell ATM Deletion

Probe specification

• ATM, 11q22.3, Red
• D11Z1, 11p11.1-q11.1, Green

The ATM probe is 182kb, labelled in red, and covers the telomeric end of the NPAT gene and the centromeric end of the ATM gene to just beyond the D11S3347 marker. The probe mix also contains a control probe for the 11 centromere (D11Z1) labelled in green.

Probe information

The protein kinase ATM (ATM serine/threonine kinase) gene at 11q22.3, is frequently deleted in cases of B-cell chronic lymphocytic leukaemia (CLL). ATM is an important checkpoint gene involved in the management of cell damage. Its function is to assess the level of DNA damage in the cell and attempt repair by phosphorylating key substrates involved in the DNA damage response pathway¹.

B-CLL is the most common leukaemia in adults; its course can vary from very indolent to rapidly progressive. Due to the low mitotic activity of the leukaemic cells in vitro, clonal chromosomal abnormalities are detected in 40-50%² of cases by conventional cytogenetics using B- cell mitogens, whereas FISH analysis identifies chromosomal aberrations in approximately 80%² of B-CLLs. Screening for deletions of ATM and/or TP53 is vital to allow informed therapy choices for B-CLL patients, as deletions of TP53 and ATM confer poorer prognosis in this disease4; therefore, the use of FISH has proved to be a powerful tool in both the diagnosis and management of patients with B-CLL^2,3,4.

Analysis of the ATM/TP53 interaction in B-CLL has shown that TP53 and ATM play an important role in the proliferation of lymphoid cancer¹. It has been shown that ATM enhances the phosphorylation of TP53, should the damage be so great that the cell requires destruction by apoptosis (which is mediated by TP53). Deletion of ATM removes this checkpoint activity and hence activation of TP53. Thus, there is no attempt made to repair, or apoptosis of, damaged cells, despite the presence of TP53. In the absence of ATM, damaged cells are allowed to continue to proliferate⁵.