Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13).

Abstract

Chromosome 8p11-12 is the site of a recurrent breakpoint in a myeloproliferative disorder that involves lymphoid (T- or B-cell), myeloid hyperplasia and eosinophilia, and evolves toward acute leukemia. This multilineage involvement suggests the malignant transformation of a primitive hematopoietic stem cell. In this disorder, the 8p11-12 region is associated with three different partners 6q27, 9q33, and 13q12. We describe here the molecular characterization of the t(8;13) translocation that involves the FGFR1 gene from 8p12, encoding a tyrosine kinase receptor for members of the fibroblast growth factor family, and a gene from 13q12, tentatively named FIM (Fused In Myeloproliferative disorders). FIM is related to DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1; this defines a gene family involved in different human pathologies. The two reciprocal fusion transcripts, FIM/FGFR1 and FGFR1/FIM are expressed in the malignant cells. The FIM/FGFR1 fusion protein contains the FIM putative zinc finger motifs and the catalytic domain of FGFR1. We show that it has a constitutive tyrosine kinase activity.

• Authors: C Popovici, J Adélaïde, V Ollendorff, M Chaffanet, G Guasch, M Jacrot, D Leroux, D Birnbaum, M J Pébusque
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 95 Issue 10 Pg. 5712-7 (May 12 1998) ISSN: 0027-8424 [Print] United States
• PMID: 9576949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FIM protein, Antirrhinum majus
• Plant Proteins
• Receptors, Fibroblast Growth Factor
• Recombinant Fusion Proteins
• Fibroblast Growth Factors
• FGFR1 protein, human
• Fgfr1 protein, mouse
• Receptor Protein-Tyrosine Kinases
• Receptor, Fibroblast Growth Factor, Type 1

Topics

• 3T3 Cells
• Amino Acid Sequence
• Animals
• Base Sequence
• Catalysis
• Chromosomes, Human, Pair 8
• Fibroblast Growth Factors (metabolism)
• Humans
• In Situ Hybridization, Fluorescence
• Introns
• Mice
• Molecular Sequence Data
• Myeloproliferative Disorders (genetics)
• Plant Proteins (genetics)
• Receptor Protein-Tyrosine Kinases
• Receptor, Fibroblast Growth Factor, Type 1
• Receptors, Fibroblast Growth Factor (genetics)
• Recombinant Fusion Proteins (genetics)
• Sequence Alignment
• Translocation, Genetic
• Tumor Cells, Cultured
• Zinc Fingers