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LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome

Leukemia volume 23, pages 1359–1361 (2009)Cite this article

Hematological malignancies associated with FGFR1 rearrangements (8p11-chromosome eighth-myeloproliferative syndrome (EMS) are rare atypical chronic myeloproliferative disorders that are in most cases associated with eosinophilia and T-cell proliferation. Clinically, EMS is an aggressive disease with a short chronic phase leading to rapid transformation into acute myeloid leukemia. The only effective treatment to date is allogenic stem cell transplantation. The genetic hallmark of this pathology is a recurrent chromosomal 8p11 rearrangement that fuses the tyrosine kinase domain of the fibroblast growth factor receptor 1 gene (FGFR1) to different gene partners. To date, nine FGFR1 partners have been identified in patients with EMS: ZMYM2/ZNF198 at 13q12, FGFR1OP/FOP at 6q27, CEP110/CEP1 at 9q33, BCR at 22q11, FGFR1OP2 at 12p11, TRIM24/TIF1 at 7q34, MYO18A at 17q23, CPSF6 at 12q15 and a human endogenous retroviral sequence, HERV-K at 19q13.3. Here, we report the identification of a tenth FGFR1 partner gene in a case of EMS associated with a t(2;8)(q37;p11) translocation.

The patient, an 82-year-old man, was referred to our department in May 2002 for pancytopenia with hemoglobin level of 10 g per 100 ml, a white blood cell count of 2.4 × 109/l and a platelet count of 40 × 109/l. Bone marrow aspiration showed a refractory anemia with an excess of blasts (15%). Cytogenetical analysis was not performed at that time. Between 2002 and 2007, the white blood cell count remained stable and the patient was occasionally treated with red blood cell transfusion depending on the hemoglobin levels (see Table 1 for evolution of blood counts). In September 2007, the white blood cell count increased to 20 × 109/l with 10% eosinophils, 2–4% myelocytes and metamyelocytes, and 8% circulating blasts. Bone marrow aspiration was hypocellular with moderate dysgranulopoiesis and 15% blasts. The presence of dacryocytes on blood smears suggested some degree of myelofibrosis. In May 2008, a new blood count showed a decrease in hemoglobin levels (8 g per 100 ml) and a stable white blood cell count with an increase in blasts (42%), attesting to the transformation into acute myeloid leukemia. Supportive care with red blood cell transfusions permitted outpatient care at first, but the patient died 1 year later.

Table 1 Patient blood counts during disease progress
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Authors and Affiliations

  1. Service de Cytogénétique, Assistance Publique-Hôpitaux de Paris, Necker-Enfants Malades Hospital, Paris, France

    G Soler, S Nusbaum, M Vekemans, S P Romana & I Radford-Weiss

  2. School of Medicine, Université Paris Descartes, Paris, France

    G Soler, B Varet, E A Macintyre, M Vekemans & S P Romana

  3. Service d’Hématologie Clinique, Assistance Publique-Hôpitaux de Paris, Necker-Enfants Malades Hospital, Paris, France

    B Varet

  4. Laboratoire Central d’Hématologie Biologique, Assistance Publique-Hôpitaux de Paris, Necker-Enfants Malades Hospital, Paris, France

    E A Macintyre

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Correspondence to S P Romana.

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Soler, G., Nusbaum, S., Varet, B. et al. LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome. Leukemia 23, 1359–1361 (2009). https://doi.org/10.1038/leu.2009.79

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