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ATM Deletion

Applications
haematology
Catalogue Numbers
LPH 011-S (5 tests)
LPH 011 (10 tests)

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-CLL2,3,4.

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.

In our hands, Cytocell FISH probes, have proven to be of the highest quality with bright, easy to interpret signals, thus providing confidence in our results. Cytocell’s customer support is outstanding, as their staff are extremely knowledgeable and truly care about their customers and their customers’ needs. Jennie Thurston, Director of Cytogenetics at Carolinas Pathology Group 

References

  1. Stankovic et al., Blood 2004;103(1):291-300
  2. Dohner et al., N Eng J Med 2000;343:1910-1916
  3. Zent et al., Blood 2010;115(21):4154-4155
  4. Rossi et al., Blood 2013;121(8):1403-1412
  5. Khanna et al., Nature Genetics 1998;20(4):398-400
  6. Arsham, MS., Barch, MJ. and Lawce HJ. (eds.) (2017) The AGT Cytogenetics Laboratory Manual. New Jersey: John Wiley & Sons Inc.
  7. Mascarello JT, Hirsch B, Kearney HM, et al. Section E9 of the American College of Medical Genetics technical standards and guidelines: fluorescence in situ hybridization. Genet Med. 2011;13(7):667-675.
  8. Wiktor AE, Dyke DLV, Stupca PJ, Ketterling RP, Thorland EC, Shearer BM, Fink SR, Stockero KJ, Majorowicz JR, Dewald GW. Preclinical validation of fluorescence in situ hybridization assays for clinical practice. Genetics in Medicine. 2006;8(1):16–23.

Microscope Images

ATM Deletion magnified
Area of Interest*
CLL

Disclaimer

This product is intended to be used on Carnoy’s solution (3:1 methanol/acetic acid) fixed haematological samples.

*Disease information supported by the literature and is not a reflection of the intended purpose of this product.