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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice

Author

  • 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
Show all

Summary, in 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)

Department/s

  • Division of Clinical Genetics
  • Division of Molecular Medicine and Gene Therapy
  • Department of Laboratory Medicine
  • Tumor microenvironment
  • Translational Genomic and Functional Studies of Leukemia
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2010

Language

English

Pages

2103-2111

Publication/Series

Blood

Volume

116

Issue

12

Document type

Journal article

Publisher

American Society of Hematology

Topic

  • Hematology

Status

Published

Research group

  • Translational Genomic and Functional Studies of Leukemia

ISBN/ISSN/Other

  • ISSN: 1528-0020