FIBROBLAST GROWTH-FACTOR RECEPTOR 1 IS USED TO FIM IN STEM-CELL MYELOPROLIFERATIVE DISORDER WITH T(8-13)(P12-Q12)

Chromosome 8p11-12 is the site of a recurrent breakpoint in a myelopro liferative disorder that involves lymphoid (T- or B-cell), myeloid hyp erplasia and eosinophilia, and evolves toward acute leukemia, This mul tilineage involvement suggests the malignant transformation of a primi tive hematopoietic stem cell. In this disorder, the 8p11-12 region is associated with three different partners 6q27, 9q33, and 13q12. We des cribe here the molecular characterization of the t(8;13) translocation that involves the FGFR1 gene from 8p12, encoding a tyrosine kinase re ceptor for members of the fibroblast growth factor family, and a gene from 13q12, tentatively named FIM (Fused In Myeloproliferative disorde rs). FIM is related to DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1; this defines a gene family involved in differen t human pathologies, The two reciprocal fusion transcripts, FIM/FGFR1 and FGFR1/FIM are expressed in the malignant cells, The FIM/FGFR1 fusi on protein contains the FIM putative zinc finger motifs and the cataly tic domain of FGFR1. We show that it has a constitutive tyrosine kinas e activity.