Recurrent CEP85L-PDGFRB fusion in patient with t(5;6) and imatinib-responsive myeloproliferative neoplasm with eosinophilia

Abstract Fusion genes involving the catalytic domain of tyrosine kinases (TKs) play an important role in the pathogenesis of hematological malignancies and solid tumors. In BCR-ABL1-negative myeloproliferative neoplasms (MPNs) several different tyrosine kinase fusion events have been described, most...

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Bibliographic Details
Published in:Leukemia & lymphoma 2013-07, Vol.54 (7), p.1527-1531
Main Authors: Winkelmann, Nils, Hidalgo-Curtis, Claire, Waghorn, Katherine, Score, Joannah, Dickinson, Helen, Jack, Andrew, Ali, Sahra, Cross, Nicholas C. P.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antineoplastic Agents - therapeutic use
Base Sequence
Benzamides - therapeutic use
CEP85L
Chromosome Breakpoints
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 6
eosinophilia
Eosinophilia - complications
Humans
imatinib
Imatinib Mesylate
Male
Middle Aged
Myeloproliferative Disorders - complications
Myeloproliferative Disorders - drug therapy
Myeloproliferative Disorders - genetics
myeloproliferative neoplasm
Oncogene Proteins, Fusion - genetics
PDGFRB
Piperazines - therapeutic use
Protein Kinase Inhibitors - therapeutic use
Pyrimidines - therapeutic use
Receptor, Platelet-Derived Growth Factor alpha - genetics
Receptor, Platelet-Derived Growth Factor beta - genetics
translocation
Translocation, Genetic
Treatment Outcome
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Summary:Abstract Fusion genes involving the catalytic domain of tyrosine kinases (TKs) play an important role in the pathogenesis of hematological malignancies and solid tumors. In BCR-ABL1-negative myeloproliferative neoplasms (MPNs) several different tyrosine kinase fusion events have been described, most commonly involving the genes encoding the platelet-derived growth factor receptor alpha (PDGFRA) or beta (PDGFRB). Since the introduction of small molecule kinase inhibitors, TK fusions have emerged as prime therapeutic targets. Here, we report a recurrent CEP85L-PDGFRB fusion in a patient with eosinophilia and an MPN. The fusion was confirmed by specific amplification of the genomic breakpoints and reverse transcription polymerase chain reaction (PCR). The patient was treated with imatinib and achieved hematologic and cytogenetic remission. Minimal residual disease screening over 3 years with nested PCR failed to detect CEP85L-PDGFRB mRNA or genomic DNA, confirming a long-term molecular remission on imatinib.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428194.2012.753544