Negative regulation of hematopoiesis by the fused in myeloproliferative disorders gene product

Hirofumi Inoue; Ikuo Nobuhisa; Keisuke Okita; Makiko Takizawa; Marie Josèphe Pébusque; Tetsuya Taga

doi:10.1016/j.bbrc.2003.11.097

Negative regulation of hematopoiesis by the fused in myeloproliferative disorders gene product

Biochem Biophys Res Commun. 2004 Jan 2;313(1):125-8. doi: 10.1016/j.bbrc.2003.11.097.

Authors

Hirofumi Inoue¹, Ikuo Nobuhisa, Keisuke Okita, Makiko Takizawa, Marie Josèphe Pébusque, Tetsuya Taga

Affiliation

¹ Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

PMID: 14672707
DOI: 10.1016/j.bbrc.2003.11.097

Abstract

The t(8;13) translocation, found in a rare and aggressive type of stem cell myeloproliferative disorder, leads to the generation of a fusion protein between the N-terminal gene product of fused in myeloproliferative disorders (FIM)/ZNF198 and the fibroblast growth factor receptor 1 (FGFR1) kinase domain. The chimeric protein was reported to have constitutively activated tyrosine kinase activity. However, little is known about a role of FIM in hematopoietic cell regulation. Here we show that FIM protein is ubiquitously expressed in mouse embryonic tissues but much less in hematopoietic cells. We also show that forced expression of FIM inhibits the emergence of hematopoietic cells in the cultured mouse aorta-gonad-mesonephros (AGM) region on embryonic day (E) 11.5, where definitive hematopoiesis is first found during embryogenesis. These results suggest that the expression level of FIM determines the development of hematopoiesis during mouse ontogeny.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aorta / cytology
Aorta / embryology
Cell Adhesion
Cells, Cultured
Core Binding Factor Alpha 2 Subunit
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / biosynthesis
GATA2 Transcription Factor
Gene Expression
Gene Expression Regulation, Developmental
Gonads / cytology
Gonads / embryology
Hematopoiesis / physiology*
Humans
Mice
Myeloproliferative Disorders / genetics*
Proto-Oncogene Proteins*
Receptor Protein-Tyrosine Kinases / genetics*
Receptor, Fibroblast Growth Factor, Type 1
Receptors, Fibroblast Growth Factor / genetics*
Recombinant Fusion Proteins / physiology*
Transcription Factors / antagonists & inhibitors
Transcription Factors / biosynthesis

Substances

Core Binding Factor Alpha 2 Subunit
DNA-Binding Proteins
GATA2 Transcription Factor
GATA2 protein, human
Gata2 protein, mouse
Proto-Oncogene Proteins
RUNX1 protein, human
Receptors, Fibroblast Growth Factor
Recombinant Fusion Proteins
Runx1 protein, mouse
Transcription Factors
FGFR1 protein, human
Fgfr1 protein, mouse
Receptor Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 1