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Product summary

  • Technology FISH
  • Application Haematology
  • Areas of interest CLL
  • Region 11q22.3
    12p11.1-q11.1
    13q14.2 / 13q34
    17p13.1
  • Label      
  • Product No. LPH 067 (2x10 tests)
    LPH 067-S (2x5 tests)
  • Intended use In vitro diagnostic. 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.

Overview

The CLL PROFILER Kit is intended to detect deletions of TP53, ATM and D13S319, and gains of the chromosome 12 centromere sequences in peripheral blood or bone marrow samples from patients with chronic lymphocytic leukaemia (CLL).

 

P53 (TP53)/ATM Probe Combination

The TP53 (tumor protein p53) gene at 17p13.1 is one of most important tumour suppressor genes; it acts as a potent transcription factor with fundamental role in the maintenance of genetic stability. Loss of TP53 is reported in 10% of patients with CLL, and is considered to be the poorest prognostic marker in that disease1,2. The ATM (ATM serine/threonine kinase) gene at 11q22.3 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 pathway3. Loss of ATM is reported in 18% of patients with CLL, and is considered a poor prognostic marker in that disease4. Analysis of the ATM/TP53 interaction in CLL has shown that TP53 and ATM play an important role in the proliferation of lymphoid cancer3. 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.

 

D13S319/13qter/12cen Deletion/Enumeration

Deletions affecting 13q14 are also the most frequent structural genetic aberrations in chronic lymphocytic leukaemia (CLL)6,7,8. This region is found to be heterozygously deleted in 30-60% and homozygously deleted in 10-20% of CLL patients9. The survival rate has been shown to be similar for the two groups10. Patients with 13q14 deletions are classified as very low risk, in the absence of any other genetic lesions1. Two non-coding RNA genes, DLEU1 (deleted in lymphocytic leukemia 1) and DLEU2 (deleted in lymphocytic leukemia 2), plus the genetic marker D13S319, span the pathogenic critical region of 13q1411. DLEU1 is considered to be the most likely CLL-associated candidate tumour suppressor gene within the 13q14 region12. Trisomy 12 is a recurrent abnormality in CLL, seen in 20% of the cases13 and often appears as the unique cytogenetic aberration (40-60% of cases with trisomy 12)7. Patients with trisomy 12 are classified as low-risk in the absence of any other genetic lesions1.

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References

  1. Rossi D, et al. Blood. 2013 Feb 21;121(8):1403-12
  2. Baliakas P, et al. Leukemia. 2014;(April):1-8
  3. Stankovic et al., Blood 2004;103(1):291-300
  4. Dohner et al., N Eng J Med 2000;343:1910-1916
  5. Khanna et al., Nature Genetics 1998;20(4):398-400
  6. Juliusson G et al., N Eng J Med 1990;323:720-4
  7. Puiggros et al., Biomed Res Int 2014;1-13
  8. Kasar et al., Nature Communications 2015;6:1-12
  9. Hammarsund M et al., FEBS Letters 2004;556:75-80
  10. Van Dyke DL et al., Br J Haematology 2009;148:544-50
  11. Liu Y et al., Oncogene 1997;15:2463-73
  12. Wolf S et al., Hum Mol Genet 2001;10:1275-85
  13. Swerdlow et al.,(eds,) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, Lyon, France, 4th edition, IARC,2017

Recommended protocol for CytoCell haematology FISH

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Sample and slide preparation

Sample and slide preparation Thumbnail
  • Spot the cell sample onto a glass microscope slide. Allow to dry.
  • Immerse the slide in 2x Saline Sodium Citrate (SSC) for 2 minutes at room temperature (RT) without agitation.
  • Dehydrate in an ethanol series (70%, 85% and 100%), each for 2 minutes at RT.
  • Allow to dry.
Haematology FISH protocol Video Image
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Haematology FISH protocol

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