Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution

Chromosomal translocations involving band 5q31-35 occur in several hematologic disorders. A clone with t(5;14)(q33; q32) translocation appeared at the relapse phase in a patient with acute myelogenous leukemia who exhibited a sole chromosomal translocation, t(7;11), at initial diagnosis. After the appearance of this clone, the leukemia progressed with marked eosinophilia, and combination chemotherapy was ineffective. Southern blot analysis showed a rearrangement of the platelet-derived growth factor receptor beta (PDGFR beta) gene at 5q33 which was not observed at initial diagnosis. This translocation resulted in a chimeric transcript fusing the PDGFR beta gene on 5q33 with a novel gene, CEV14, located at 14q32. Expression of the 5' region of the PDGFR beta cDNA, upstream of the breakpoint, was not detected. However, the 3' region of PDGFR beta, which was transcribed as part of the CEV14-PDGFR beta fusion gene, was detected. A partial cDNA for a novel gene, CEV14, includes a leucine zipper motif and putative thyroid hormone receptor interacting domain and is expressed in a wide range of tissues, The expression of a CEV14-PDGFR beta fusion gene in association with aggressive leukemia progression suggests that this protein has oncogenic potential. (C) 1997 by The American Society of Hematology.