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Acquired Isodisomy for chromosome 13 is common in AML, and associated with FLT3-itd mutations

Leukemia volume 19, pages 2355–2358 (2005)Cite this article

TO THE EDITOR

The FMS-like tyrosine kinase 3 (FLT3) gene in chromosome band 13q12, encodes a tyrosine kinase receptor.1 FLT3 mutations are common in acute myeloid leukaemia (AML), most often an internal tandem duplication (itd), and are associated with a poor prognosis.1, 2, 3, 4, 5, 6 FLT3-itd mutations can be detected by PCR of genomic DNA.1, 3 Some patients show excess dosage of the FLT3-itd allele, or apparent complete loss of the FLT3 wild-type (wt) gene,1, 2, 3, 4, 5, 6 and this has been associated with a more adverse prognosis.3, 4, 5 The mechanism for excess dosage is not known, although cryptic deletions of the FLT3-wt region,3, 4 acquired isodisomy (AI) for chromosome 13,4 or segmental AI through homologous somatic recombination,5 have been suggested. This uncertainty with respect to the mechanism confounds analysis of prognostic impact within this potential subgroup of FLT3-itd patients as stratification without knowledge of the mechanism may be inaccurate. We investigated these mechanisms and demonstrated AI for chromosome 13 (AI-13) to be the most likely cause of FLT3-itd excess dosage.

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Acknowledgements

The authors wish to thank many of our laboratory colleagues for their contribution to the molecular genetic and cytogenetic analysis of the patients, in particular Alison Ely and Jane Bryon of the WMRGL; Fiona Brew of Affymetrix for assisting with the Affymetrix GeneChip 10k 2.0 SNP tests; and our haematology colleagues Chris Fegan, Jeff Nielson, Phil Darbyshire in Birmingham and Penny Taylor in Newcastle for their clinical contribution.

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Authors and Affiliations

  1. West Midlands Region Genetics Laboratory, Birmingham Women's Hospital, Edgbaston, Birmingham, UK

    M Griffiths, J Mason, M Rindl, S Akiki, D McMullan & V Stinton

  2. Regional Genetics Service, Institute of Human Genetics, Central Parkway, Newcastle upon Tyne, UK

    H Powell, A Curtis & N Bown

  3. Haematology Department, University Hospital of Birmingham, Birmingham, UK

    C Craddock

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  1. M Griffiths
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  2. J Mason
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Correspondence to M Griffiths.

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Griffiths, M., Mason, J., Rindl, M. et al. Acquired Isodisomy for chromosome 13 is common in AML, and associated with FLT3-itd mutations. Leukemia 19, 2355–2358 (2005). https://doi.org/10.1038/sj.leu.2403988

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