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Association with the single-nucleotide polymorphism (Glu785Lys) of the granulocyte colony-stimulating factor receptor with myelodysplastic syndromes and acute myeloid leukemia with multlineage dysplasia

Leukemia volume 20, pages 2188–2189 (2006)Cite this article

Myelodysplastic syndromes (MDSs) comprise a heterogeneous group of disorders. Although our understanding of the pathophysiology of this disease has been greatly improved within recent years, the underlying factors relevant for the development of MDS have not been identified yet. Wölfler et al.1 have recently shown that a single-nucleotide polymorphism (SNP) of the cytoplasmic domain of the granulocyte colony-stimulating factor (G-CSF) receptor at position 785 (G-CSF-R_Glu785Lys) predisposes for the development of high-risk MDS as defined by more than 5% marrow blasts. As a matter of fact, the SNP was detected in 7/72 (9.7%) of MDS patients, including five patients with secondary acute myeloid leukemia (AML) derived from MDS, compared to a frequency of 0.9% in normal controls. Interestingly, further analyses revealed the occurrence of the SNP in only 2.4% of patients with de novo AML (n=84). Together with in vitro experiments, showing that this SNP results in the inhibition of colony formation of G-CSF-receptor-deficient mice progenitor cells when exposed to G-CSF, the authors concluded that this new constitutional polymorphism renders normal individuals at increased risk of high-risk MDS.

Recently, the WHO defined several new categories of AML2 including AML with multilineage dysplasia (AML-MD), which displays dysplastic features in bone marrow as seen in patients with MDS. We speculated whether this SNP occurs more frequently in this new category, which has been underrepresented in the report by Wölfler et al.1 We therefore analyzed a larger cohort of AML patients (n=445) including 346 patients with AML-MD treated within the AML-SHG 96 study.3 Given the increased risk of high-risk MDS in patients carrying the polymorphism, we further investigated 80 MDS patients including a defined (n=21) population (refractory anemia: n=4, RA with excess blast (RAEB): n=10; RAEB in transformation: n=7) with a documented interval (median 7.1 months, range 0.2–73) from diagnosis to progression to AML from the Düsseldorf MDS registry. The patient characteristics are provided in Table 1.

Table 1 Patient characteristics
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Figure 1

References

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Acknowledgements

We thank Marika Karger, Ulrike Löwel, Marita Hartwig and Peggy Grassmel for excellent technical assistance.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany

    U Platzbecker, U Schäkel, T Illmer, S Soucek, M Schaich, G Ehninger & C Thiede

  2. Klinik für Hämatologie, Onkologie und Klinische Immunologie, Heinrich Heine Universität, Düsseldorf, Germany

    U Germing

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  1. U Platzbecker
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  2. U Germing
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  3. U Schäkel
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Correspondence to U Platzbecker.

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Platzbecker, U., Germing, U., Schäkel, U. et al. Association with the single-nucleotide polymorphism (Glu785Lys) of the granulocyte colony-stimulating factor receptor with myelodysplastic syndromes and acute myeloid leukemia with multlineage dysplasia. Leukemia 20, 2188–2189 (2006). https://doi.org/10.1038/sj.leu.2404399

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