Fusion of H4/D10S170 to the platelet-derived growth factor receptor beta in BCR-ABL-negative myeloproliferative disorders with a t(5;10)(q33;q21)

We have studied a patient who presented with clinical features suggestive o f chronic myeloid leukemia in accelerated phase. BCR-ABL transcripts were u ndetectable by reverse transcription-FCR, but a novel reciprocal translocat ion, t(5;10)(q33;q21,2), was seen by standard cytogenetic analysis. Chromos ome band 5q33 contains the gene encoding the platelet-derived growth factor beta receptor (PDGF beta R), the receptor tyrosine kinase that is disrupte d by the t(5;7), t(5;12), and t(5;14) in myeloid disorders, resulting in th e fusion of PDGF beta R to HIP1, TEL/ETV6, and CEV14, respectively, Souther n analysis with PDGF beta R cDNA revealed novel bands in patient but not co ntrol DNA after digestion with several restriction enzymes, indicating that this gene is also targeted by the t(5;10), Fluorescence in situ hybridizat ion analysis of chromosome 5 indicated that a small inversion at 5q33 had t aken place in addition to the interchromosomal translocation, The site of t he chromosome 10 breakpoint fell within YAC 940e4. Because all PDGF beta R fusions described thus far result in splicing to a common exon of this gene , we performed 5'-rapid amplification of cDNA ends PCR on patient RNA. Seve ral clones were isolated in which PDGF beta R fused in frame to H4/D10S170, a previously described ubiquitously expressed gene that is fused to the re t protein tyrosine kinase to form the PTC-1 oncogene in approximately 20% o f papillary thyroid carcinomas, The presence of H4-PDGF beta R chimeric mRN A in the patient was confirmed by reverse transcription-PCR; reciprocal PDG F beta R-H4 transcripts were not detected. We conclude that t(5;10)(q33;q21 .2) is a novel translocation in BCR-ABL-negative chronic myeloid leukemia a nd that this abnormality results in an H4-PDGF beta R fusion gene. This fin ding further strengthens the association between myeloproliferative disorde rs and deregulated tyrosine kinases.