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Chronic Myeloproliferative Disorders

The severity of FIP1L1–PDGFRA-positive chronic eosinophilic leukaemia is associated with polymorphic variation at the IL5RA locus

Leukemia volume 21, pages 2428–2432 (2007)Cite this article

Abstract

We have investigated the hypothesis that constitutional genetic variation in IL-5 signalling may be associated with the development or severity of FIP1L1–PDGFRA-positive chronic eosinophilic leukaemia (CEL) in humans. We genotyped six single-nucleotide polymorphisms (SNP) within or close to the IL5RA or IL5 genes in 82 patients with FIP1L1–PDGFRA-positive CEL plus, as controls, healthy individuals (n=100), patients with FIP1L1–PDGFRA-negative eosinophilia (n=100) or patients with chronic myeloid leukaemia (CML) (n=100). We found no association between SNP allele frequency between FIP1L1–PDGFRA-positive and control cases. However, for FIP1L1–PDGFRA cases, we found an association between the genotype at rs4054760, an SNP in the 5′-UTR of IL5RA and peripheral blood eosinophil count (P=0.026) as well as the presence or absence of tissue infiltration (P=0.032). Although these associations fell below the level of significance once corrected for multiple testing, no such association was seen in FIP1L1–PDGFRA-negative cases and no difference in allele frequencies for rs4054760 was seen in control populations across Europe. Furthermore, in an analysis of 112 patients with CML, IL5RA expression was strongly related to rs4054760 genotype (P<0.001). These data suggest that the variations in IL5RA expression are linked to constitutional IL5RA genotype and severity of FIP1L1–PDGFRA disease.

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Acknowledgements

SB, SK, KW and HW designed and performed the laboratory analysis; CP, KZ, CZ, DC, FBB, CW, GM and AR provided patient samples and data; NC designed and directed the study. All authors reviewed and commented on the manuscript. This work was supported by the Forschungsfoerderungsverein der Krebshilfe Oberoesterreich, Leukaemia Research (UK), the Lady Tata Memorial Trust and the ‘European LeukemiaNet’ within the 6th European Community Framework Programme for Research and Technological Development.

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Authors and Affiliations

  1. Wessex Regional Genetics Laboratory, University of Southampton, Salisbury, UK

    S Burgstaller, S Kreil, K Waghorn, H White & N C P Cross

  2. III Medizinische Universitätsklinik, Medizinische Fakultät der Universität Mannheim, Heidelberg, Germany

    G Metzgeroth, C Walz & A Reiter

  3. Laboratoire d'Hematologie A, CHU Lille, Lille, France

    C Preudhomme

  4. Foundation of Biomedical Research, Academy of Athens, Athens, Greece

    K Zoi & C Zoi

  5. Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

    D Cilloni

  6. Department of Haematology, Ealing Hospital, London, UK

    F Brito-Babapulle

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  1. S Burgstaller
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  2. S Kreil
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  3. K Waghorn
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Correspondence to N C P Cross.

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Burgstaller, S., Kreil, S., Waghorn, K. et al. The severity of FIP1L1–PDGFRA-positive chronic eosinophilic leukaemia is associated with polymorphic variation at the IL5RA locus. Leukemia 21, 2428–2432 (2007). https://doi.org/10.1038/sj.leu.2404977

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