The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia

We have cloned a fusion partner of the MLL gene at 11q23 and identified it as the gene encoding the human formin-binding protein 17, FBP17. It maps to chromosome 9q34 centromeric to ABL. The gene fusion results from a complex chromosome rearrangement that was resolved by fluorescence in situ hybridi zation with various probes on chromosomes 9 and 11 as an ins(11;9)(q23;q34) inv(11)(q13q23). The rearrangement resulted in a 5 ' -MLL/FBP17-3 ' fusion mRNA. We retrovirally transduced murine-myeloid progenitor cells with MLL/F BP17 to test its transforming ability. In contrast to MLL/ENL, MLL/ELL and other MLL-fusion genes, MLL/FBP17 did not give a positive readout in a seri al replating assay. Therefore, we assume that additional cooperating geneti c abnormalities might be needed to establish a full malignant phenotype. FB P17 consists of a C-terminal Src homology 3 domain and an N-terminal region that is homologous to the cell division cycle protein, cdc15, a regulator of the actin cytoskeleton in Schizosaccharomyces pombe. Both domains are se parated by a consensus Rho-binding motif that has been identified in differ ent Rho-interaction partners such as Rhotekin and Rhophilin. We evaluated w hether FBP17 and members of the Rho family interact in vivo with a yeast tw o-hybrid assay. None of the various Rho proteins tested, however, interacte d with FBP17. We screened a human kidney library and identified a sorting n exin, SNX2, as a protein interaction partner of FBP17. These data provide a link between the epidermal growth factor receptor pathway and an MLL fusio n protein.