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Reply to Inokuchi et al

Leukemia volume 20, page 357 (2006)Cite this article

We thank Inokuchi et al.1 for their detailed comments regarding our letter2 and appreciate the opportunity to reply. Firstly, we would like to emphasize that Inokuchi et al. performed an extensive analysis of the c-kit variants M541L and N564K, analysing clinical data from 80 patients suffering from CML and using a murine system for in vitro studies.3 In contrast, our data might be indeed limited, yet still powerful. The limitation reflects solely our aim of testing the hypothesis of whether or not the variants M541L and N564K are associated with CML in a Caucasian populations. Equal allele frequencies for 541Leu in 102 Caucasian CML patients and 166 controls (8.3 and 8.1%, respectively) and lack of the 564Lys sequence variant in all patients and controls do not support a functional importance for either variant in CML. This finding is corroborated by the low degree of conservation in various species and the data from the Sorting Intolerant From Tolerant amino-acid substitutions (SIFT) analysis, which predicted that both amino-acid changes are tolerable and therefore do not affect the function of the protein.2

We agree with Inokuchi et al.1 that ethnic differences in the allele frequencies of common sequence variations may be associated with different phenotypes, which we have observed previously,4, 5 although the reason for these differences is unknown. We cannot exclude that the same may apply for Japanese CML patients carrying c-kit variants.

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References

  1. Inokuchi K, Yamaguchi H, Tarusawa M, Futaki M, Hanawa H, Tanosaki S et al. Reply to ‘The c-kit (CD117) sequence variation M541L, but not N564K, is frequent in the general population, and is not associated with CML in Caucasians’ by Kruger et al.

  2. Kruger S, Emig M, Lohse P, Ehninger G, Hochhaus A, Schackert HK . The c-kit (CD117) sequence variation M541L, but not N564K, is frequent in the general population, and is not associated with CML in Caucasians.

  3. Inokuchi K, Yamaguchi H, Tarusawa M, Futaki M, Hanawa H, Tanosaki S et al. Abnormality of c-kit oncoprotein in certain patients with chronic myelogenous leukaemia – potential clinical significance. Leukemia 2002; 16: 170–177.

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  4. Krex D, Ziegler A, Schackert HK, Schackert G . Lack of association between endoglin intron 7 insertion polymorphism and intracranial aneurysms in a white population: evidence of racial/ethnic differences. Stroke 2001; 32: 2689–2694.

    Article  CAS  Google Scholar 

  5. Krex D, Konig IR, Ziegler A, Schackert HK, Schackert G . Extended single nucleotide polymorphism and haplotype analysis of the elastin gene in Caucasians with intracranial aneurysms provides evidence for racially/ethnically based differences. Cerebrovasc Dis 2004; 18: 104–110.

    Article  CAS  Google Scholar 

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Author notes

  1. S Krüger

    Present address: Institute of Clinical Genetics, Dresden University of Technology, Dresden, Germany

Authors and Affiliations

  1. Department of Surgical Research, Dresden University of Technology, Dresden, Germany

    S Krüger & H K Schackert

  2. III. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany

    M Emig & A Hochhaus

  3. Department of Clinical Chemistry – Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany

    P Lohse

  4. I. Department of Internal Medicine, Dresden University of Technology, Dresden, Germany

    G Ehninger

Authors
  1. S Krüger
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  2. M Emig
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  3. P Lohse
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  4. G Ehninger
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  5. A Hochhaus
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  6. H K Schackert
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Krüger, S., Emig, M., Lohse, P. et al. Reply to Inokuchi et al. Leukemia 20, 357 (2006). https://doi.org/10.1038/sj.leu.2404041

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