title: The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA.
abstract: Chronic myeloid leukaemia (CML) is characterized by the presence of the BCR-ABL fusion gene, usually in association with the t(9;22)(q34;q11) translocation. We report here the identification and cloning of a rare variant translocation, t(4;22)(q12;q11), in two patients with a CML-like myeloproliferative disease (MPD). RT-PCR indicated that both patients were negative for BCR-ABL, but FISH analysis suggested that the BCR gene was rearranged. Since other translocations in MPDs frequently involve tyrosine kinases, we designed a multiplex PCR to search for mRNA fusions between BCR and three potential partner genes at 4q12: KIT, KDR and PDGFRA. An unusual inframe BCR-PDGFRA fusion mRNA was identified in both patients, with either BCR exon 7 or exon 12 fused to short BCR intron-derived sequences, which were in turn fused to part of PDGFRA exon 12. Sequencing of the genomic breakpoint junctions showed that the chromosome 22 breakpoints fell in BCR introns whereas the chromosome 4 breakpoints were within PDGFRA exon 12. This is the first report of a fusion gene that involves PDGFRA. Our findings indicate that apparently simple cytogenetic variants of t(9;22) do not always mask a cryptic BCR-ABL fusion, even when found in association with clinical and haematological indications of CML.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK.
authors.forename: E Joanna
authors.initials: EJ
authors.lastname: Baxter
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Pascual
authors.initials: P
authors.lastname: Bolufer
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.forename: José M
authors.initials: JM
authors.lastname: Fernandez
authors.forename: Leonor
authors.initials: L
authors.lastname: Senent
authors.forename: José
authors.initials: J
authors.lastname: Cervera
authors.forename: Federico
authors.initials: F
authors.lastname: Moscardo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D000328:Adult; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D002894:Chromosomes, Human, Pair 4; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014178:Translocation, Genetic
chemical_list: D012333:RNA, Messenger; D017479:Receptors, Platelet-Derived Growth Factor; D016044:Fusion Proteins, bcr-abl