Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice
Författare
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)
Avdelning/ar
- Avdelningen för klinisk genetik
- Avdelningen för molekylärmedicin och genterapi
- Institutionen för laboratoriemedicin
- Tumörmikromiljö
- Translationella genomiska och funktionella studier av leukemi
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2010
Språk
Engelska
Sidor
2103-2111
Publikation/Tidskrift/Serie
Blood
Volym
116
Issue
12
Dokumenttyp
Artikel i tidskrift
Förlag
American Society of Hematology
Ämne
- Hematology
Status
Published
Forskningsgrupp
- Translational Genomic and Functional Studies of Leukemia
ISBN/ISSN/Övrigt
- ISSN: 1528-0020