ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain

An acquired chromosomal translocation, t(8;13)(p11;q11-12), observed in a d istinctive type of stem cell leukemia/lymphoma syndrome, leads to the fusio n of the 5' portion of ZNF198 and the 3' portion of FGFR1. ZNF198-FGFR1 fus ion transcripts encode 4 to 10 zinc fingers, a proline-rich region, and the intracellular portion of the FGFR1 (fibroblast growth factor receptor 1) r eceptor tyrosine kinase, We demonstrate that the ZNF198 proline-rich region constitutes a novel self-association domain. When fused to the intracellul ar domain of FGFR1, the ZNF198 proline-rich region is sufficient to cause o ligomerization, FGFR1 tyrosine kinase activation, and transformation of Ba/ F3 cells to IL-3 independent growth.