Novel fusion between the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with chronic myeloid leukemia-like neoplasm: undetectable residual disease after imatinib therapy

Eur J Haematol. 2015 Nov;95(5):480-3. doi: 10.1111/ejh.12576. Epub 2015 May 20.

Abstract

Rare patients suffering from myeloid neoplasms share clinical and cytological features indistinguishable from chronic myeloid leukemia (CML) but lack the BCR-ABL1 fusion gene. Several studies provide evidence that alterations in genes encoding tyrosine kinase receptors such as the platelet-derived growth factor receptor (PDGFR) may be involved in the pathogenesis of these disorders. Here we describe a patient with a rare CML-like disease in whom we identified a novel in-frame BCR-PDGFRA rearrangement joining BCR exon 17 to PDGFRA exon 13, resulting in overexpression of PDGFRA. The design of a specific quantitative PCR assay to monitor the molecular response during treatment with imatinib, a multitargeted tyrosine kinase inhibitor (TKI) with activity against ABL, c-Kit, and PDGFRA revealed an outstanding disease control with durably undetectable BCR-PDGFRA transcripts. Multiple TKIs are currently available yet with distinct target profiles; thus, accurate molecular diagnosis and monitoring tools are essential to establish tailored treatments and assess response to therapy in this type of rare hematological malignancy.

Keywords: BCR-PDGFRA; imatinib; myeloproliferative disorder.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Exons*
  • Female
  • Humans
  • Imatinib Mesylate / administration & dosage*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Neoplasm, Residual
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Proto-Oncogene Proteins c-bcr / biosynthesis
  • Proto-Oncogene Proteins c-bcr / genetics*
  • Receptor, Platelet-Derived Growth Factor alpha / biosynthesis
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*

Substances

  • Oncogene Proteins, Fusion
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor alpha
  • BCR protein, human
  • Proto-Oncogene Proteins c-bcr