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Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice

  • Helena Ågerstam
  • Marcus Järås
  • Anna Andersson
  • Petra Johnels
  • Nils Hansen
  • Carin Lassen
  • Marianne Rissler
  • David Gisselsson Nord
  • Tor Olofsson
  • Johan Richter
  • Xiaolong Fan
  • Mats Ehinger
  • Thoas Fioretos
Publishing year: 2010
Language: English
Pages: 2103-2111
Publication/Series: Blood
Volume: 116
Issue: 12
Document type: Journal article
Publisher: American Society of Hematology

Abstract english

The 8p11 myeloproliferative syndrome (EMS), also referred to as stem cell leukemia/lymphoma, is a chronic myeloproliferative disorder that rapidly progresses into acute leukemia. Molecularly, EMS is characterized by fusion of various partner genes to the FGFR1 gene, resulting in constitutive activation of the tyrosine kinases in FGFR1. To date, no previous study has addressed the functional consequences of ectopic FGFR1 expression in the potentially most relevant cellular context, that of normal primary human hematopoietic cells. Herein, we report that expression of ZMYM2/FGFR1 (previously known as ZNF198/FGFR1) or BCR/FGFR1 in normal human CD34(+) cells from umbilicalcord blood leads to increased cellular proliferation and differentiation toward the erythroid lineage in vitro. In immunodeficient mice, expression of ZMYM2/FGFR1 or BCR/FGFR1 in human cells induces several features of human EMS, including expansion of several myeloid cell lineages and accumulation of blasts in bone marrow. Moreover, bone marrow fibrosis together with increased extramedullary hematopoiesis is observed. This study suggests that FGFR1 fusion oncogenes, by themselves, are capable of initiating an EMS-like disorder, and provides the first humanized model of a myeloproliferative disorder transforming into acute leukemia in mice. The established in vivo EMS model should provide a valuable tool for future studies of this disorder. (Blood. 2010;116(12):2103-2111)


  • Hematology


  • ISSN: 1528-0020
Thoas Fioretos
E-mail: thoas.fioretos [at]

Principal investigator

Division of Clinical Genetics

+46 46 222 45 95

+46 70 334 33 67