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

Proc Natl Acad Sci U S A. 1998 May 12;95(10):5712-7. doi: 10.1073/pnas.95.10.5712.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • 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

Associated data

  • GENBANK/Y13472