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A novel ETV6-PDGFRB fusion transcript missed by standard screening in a patient with an imatinib responsive chronic myeloproliferative disease

Leukemia volume 21, pages 1839–1841 (2007)Cite this article

ETV6-PDGFRB results from the t(5;12)(q31–33;p13) and, although rare, is the most frequent of at least 15 known PDGFRB fusion genes. ETV6-PDGFRB is usually seen in patients with chronic myelomonocytic leukaemia, atypical chronic myeloid leukaemia (aCML) or chronic eosinophilic leukaemia (CEL), with most patients exhibiting peripheral blood or bone marrow eosinophilia. Although ETV6-PDGFRB disease may be controlled with conventional therapy (hydroxyurea, busulphan, interferon-α), many die from transformed disease or other causes. More recently, however, imatinib has emerged as the standard therapy for PDGFR-rearranged patients, with most experiencing sustained haematologic and cytogenetic remission, and many achieving molecular remission.1 Molecular confirmation of a PDGFR rearrangement is therefore important for appropriate clinical management and monitoring response to therapy. For the t(5;12)(q31–33;p13), confirmation of the presence of ETV6-PDGFRB is particularly important since many cases with this translocation have a distinct molecular aetiology, with upregulation of IL-3 expression and no involvement of PDGFRB.2

In the great majority of positive cases, ETV6 exon 4 splices to PDGFRB exon 11 and is typically detected by reverse transcription PCR (RT-PCR) using primers directed to ETV6 exon 3 or 4 and PDGFRB exon 11. Out of 10 positive cases we have detected with these primer combinations, only one had a variant fusion in which ETV6 exon 4 was fused to PDGFRB exon 9 (unpublished data). Recently, a patient with idiopathic myelofibrosis and an ETV6 exon 7–PDGFRB exon 10 fusion was reported and it was suggested that this novel transcript may have accounted for the somewhat unusual clinical phenotype seen in this case.3 Importantly, both these variants are detectable using the standard primer sets above. Here we report a novel ETV6-PDGFRB fusion with breakpoints outside this region.

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Acknowledgements

This work was supported by Leukaemia Research (UK).

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Authors and Affiliations

  1. Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK

    C E Curtis, F H Grand, K Waghorn & N C P Cross

  2. Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India

    T P Sahoo & J George

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  1. C E Curtis
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  2. F H Grand
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Correspondence to N C P Cross.

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Curtis, C., Grand, F., Waghorn, K. et al. A novel ETV6-PDGFRB fusion transcript missed by standard screening in a patient with an imatinib responsive chronic myeloproliferative disease. Leukemia 21, 1839–1841 (2007). https://doi.org/10.1038/sj.leu.2404728

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