Fusion of the Platelet-Derived Growth Factor Receptor β to a Novel Gene CEV14 in Acute Myelogenous Leukemia After Clonal Evolution

Abstract

AbstractChromosomal translocations involving band 5q31-35 occur in several hematologic disorders. A clone with a 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 β (PDGFRβ) gene at 5q33 which was not observed at initial diagnosis. This translocation resulted in a chimeric transcript fusing the PDGFRβ gene on 5q33 with a novel gene, CEV14, located at 14q32. Expression of the 5′ region of the PDGFRβ cDNA, upstream of the breakpoint, was not detected. However, the 3′ region of PDGFRβ, which was transcribed as part of the CEV14-PDGFRβ 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-PDGFRβ fusion gene in association with aggressive leukemia progression suggests that this protein has oncogenic potential.