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A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm

Leukemia volume 27, pages 1186–1188 (2013)Cite this article

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The eight p11 (8p11) myeloproliferative syndrome (EMS) term is designated in the 2008 World Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissues1 as myeloid and lymphoid neoplasms with eosinophilia and abnormalities of fibroblast growth factor receptor 1 gene (FGFR1). These aggressive malignancies are characterized by their rare occurrence, heterogeneity, eosinophilia and rapid progression in acute myeloid leukemia. The fibroblast growth factor receptor 1 gene (FGFR1) encodes for a tyrosine kinase receptor for fibroblast growth factor and is known to be fused to different recurrent gene partners, such as TPR2 (1q25), LRRFIP1 (2q37), FGFR1OP1 (6q27), CUX1(ref.3) (7q22), TRIM24 (7q34), CEP110 (9q33), FGFR1OP2 (12p11), CPSF6 (12q15), ZNF198 (13q12), MYO18A (17q23), HERV-K (19q13) and BCR (22q11), reviewed in Jackson et al.4 In all cases the chimeric protein contains an aberrant tyrosine kinase domain constitutively activated. Treatments, including tyrosine kinase inhibitors based regimen, are often ineffective so that FGFR1 abnormalities are associated with bad prognosis. The few long-term survivors have undergone stem cell allograft.

We report here a novel partner gene for FGFR1, identified in a 63-year old Caucasian female. The patient was referred to our institution for dyspnea, impaired general condition and splenomegaly without hepatomegaly nor adenopathy. Medical history included a severe stroke following the rupture of a cerebral aneurysm, a mitral valve replacement and an ischemic cardiopathy. Peripheral blood examination showed hemoglobin level of 101 g/l, a platelet count of 65 × 109/l and a white blood cell count of 311 × 109/l with 44% neutrophils (136 × 109/l), 3% eosinophils (3 × 109/l), 2% monocytes (6.2 × 109/l), 46% promyelocytes, myelocytes and metamyelocytes and 2% circulating blasts. Bone marrow aspiration stained with May Grünwald Giemsa was hypercellular, with granular hyperplasia, dysgranulopoiesis and few eosinophils. The diagnosis of myeloproliferative/myelodysplastic syndrome was retained at that time because of the proliferative features, with dysplasia and very few monocytes in the bone marrow. Molecular analysis did not found any V617F or exon 12 mutation in JAK2, nor BCR-ABL1 fusion transcripts.

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Acknowledgements

We thank Dr Elisabeth FLORI for providing part of the BACs.

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Authors and Affiliations

  1. Pôle de Biologie, Laboratoire d’Hématologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    C Gervais, L Dano, C Hélias, A-C Galoisy, A Ittel & L Mauvieux

  2. Laboratoire Régional de Cytogénétique Hématologique d’Alsace Mulhouse–Strasbourg, Strasbourg, France

    C Gervais, L Dano, C Hélias, E Jeandidier, A Ittel & L Mauvieux

  3. Plateforme Régionale INCa de Génétique Moléculaire des Cancers d’Alsace, Strasbourg, France

    C Gervais, L Dano, C Hélias, E Jeandidier, A-C Galoisy, A Ittel & L Mauvieux

  4. Laboratoire d’Hématologie Cellulaire, Faculté de Médecine de Strasbourg, Strasbourg, France

    N Perrusson & L Mauvieux

  5. Département d’Onco-Hématologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    R Herbrecht & K Bilger

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  1. C Gervais
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Correspondence to L Mauvieux.

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Gervais, C., Dano, L., Perrusson, N. et al. A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm. Leukemia 27, 1186–1188 (2013). https://doi.org/10.1038/leu.2012.286

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