Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

ATM variants and predisposition to childhood T-lineage acute lymphoblastic leukaemia

Leukemia volume 20, pages 526–527 (2006)Cite this article

We read with a great interest the recent study published by Meier et al.,1 on genetic variants of the ataxia telangiectasia-mutated (ATM) gene, drug resistance, clinical outcome and predisposition to childhood T-lineage acute lymphoblastic leukaemia (T-ALL). They reported a high prevalence (60%) of nucleotide substitution in 16 selected ATM exons in 103 T-ALL, but this prevalence was similar to that of the controls (52%). Interestingly, five alterations located in the coding part of ATM were found to be 2.6-fold higher in T-ALL (13%) than in controls (5%, P=0.06), associated with a higher white blood cell count at diagnosis (P=0.05) and with an increased relapse-risk (P=0.05).

As mentioned by Meier et al., 21 different ATM alterations found in 7/31 (23%) childhood T-ALL samples were reported in our article published in 2003.2 In our study, 21 different rare variants and nine different well-known polymorphisms were found in all ATM exons, but only rare variants were reported in detail. Therefore, if we considered rare variants and polymorphisms located in the 16 exons analysed by Meier et al. (exons: 9, 12, 15, 17, 19, 20, 24, 31, 32, 39, 40, 41, 47, 53, 55 and 62), similar prevalence was found with 18/31 T-ALL (58%) harbouring ATM alteration(s). In contrast to the hypothesis proposed by Meier et al., this result suggests that we have the same sensitivity to detect ATM genetic abnormalities, even if the DHPLC conditions used in the two studies were different.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Meier M, den Boer ML, Hall AG, Irving JAE, Passier M, Minto L et al. Relation between genetic variants of the ataxia telangiectasia-mutated (ATM) gene, drug resistance, clinical outcome and predisposition to childhood T-lineage acute lymphoblastic leukaemia. Leukemia 2005; 19: 1887–1895.

    Article  CAS  Google Scholar 

  2. Gumy Pause F, Wacker P, Maillet P, Betts D, Sappino AP . ATM gene alterations in childhood acute lymphoblastic leukemias. Hum Mutat 2003; 21: 554.

    Article  Google Scholar 

  3. Wiemels JL, Smith RN, Taylor GM, Eden OB, Alexander FE, Greaves MF . Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA 2001; 98: 4004–4009.

    Article  CAS  Google Scholar 

  4. Krajinovic M, Labuda D, Richer C, Karimi S, Sinnett D . Susceptibility to childhood acute lymphoblastic leukemia: influence of CYP1A1, CYP2D6, GSTM1, and GSTT1 genetic polymorphisms. Blood 1999; 93: 1496–1501.

    CAS  Google Scholar 

  5. Krajinovic M, Labuda D, Sinnett D . Glutathione S-transferase P1 genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukaemia. Pharmacogenetics 2002; 12: 655–658.

    Article  CAS  Google Scholar 

  6. Krajinovic M, Lamothe S, Labuda D, Lemieux-Blanchard R, Theoret Y, Moghrabi A et al. Role of MTHFR genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. Blood 2004; 103: 252–257.

    Article  CAS  Google Scholar 

  7. Krajinovic M, Sinnett H, Richer C, Labuda D, Sinnett D . Role of NQO1, MPO and CYP2E1 genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. Int J Cancer 2002; 97: 230–236.

    Article  CAS  Google Scholar 

  8. Mathonnet G, Krajinovic M, Labuda D, Sinnett D . Role of DNA mismatch repair genetic polymorphisms in the risk of childhood acute lymphoblastic leukaemia. Br J Haematol 2003; 123: 45–48.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the Foundations Dr Dubois-Ferrière–Dinu Lipatti (Geneva, Switzerland), Cancer & Solidarity (2003, Geneva, Switzerland (+41-22-839.11.99)) and la Fondation pour la Lutte contre le Cancer et pour des Recherches Médico-biologiques (Geneva, Switzerland) for their financial support. We are also very grateful to Dr S Hunger (COG, Grant CA30969 and CA29139) for providing samples and to Mary Khoshbeen-Boudal for her excellent technical assistance.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Unit of Hematology/Oncology, University Hospital of Geneva, Geneva, Switzerland

    F Gumy-Pause & P Wacker

  2. Division of Oncology, University Hospital of Geneva, Geneva, Switzerland

    P Maillet & A-P Sappino

  3. Department of Oncology, University Children's Hospital, Zürich, Switzerland

    D R Betts

Authors
  1. F Gumy-Pause
    View author publications

    Search author on:PubMed Google Scholar

  2. P Wacker
    View author publications

    Search author on:PubMed Google Scholar

  3. P Maillet
    View author publications

    Search author on:PubMed Google Scholar

  4. D R Betts
    View author publications

    Search author on:PubMed Google Scholar

  5. A-P Sappino
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gumy-Pause, F., Wacker, P., Maillet, P. et al. ATM variants and predisposition to childhood T-lineage acute lymphoblastic leukaemia. Leukemia 20, 526–527 (2006). https://doi.org/10.1038/sj.leu.2404091

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.leu.2404091

This article is cited by

Search

Advanced search

Quick links