Human Molecular Genetics, 2002, Vol. 11, No. 12 1391-1397
© 2002 Oxford University Press
The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA
1Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK, 2Human Genetics Division, University of Southampton School of Medicine, Southampton SO16 6YD, UK, 3III Medizinische Universitätsklinik, Klinikum Mannheim, 68305 Mannheim, Germany and 4Servicio de Hematología and 5Department of Medical Biopathology, Hospital Universitario La Fe, 46009 Valencia, Spain
Received January 17, 2002; Accepted March 25, 2002
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.
* To whom correspondence shall be addressed. Tel: +44(0) 1722 429080; Fax: +44(0) 1722 338095; Email: ncpc{at}soton.ac.uk
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