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Myeloproliferative neoplasm with ETV6-ABL1 fusion: a case report and literature review

Katya Gancheva1, Andres Virchis2, Julie Howard-Reeves3, Nick CP Cross4, Diana Brazma3, Colin Grace1, Paul Kotzampaltiris3, Fedra Partheniou3 and Elisabeth Nacheva13*

Author Affiliations

1 Leukaemia Cytogenetics, Academic Haematology, UCL Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK

2 Department of Haematology, Barnet and Chase Farm Hospitals NHS Trust, Barnet Hospital, Wellhouse Lane, Barnet, London, Hertforshire EN2 3DJ, UK

3 Leukaemia Cytogenetics, Royal Free NHS Foundation Trust, Pond Street, London NW3 2QG, UK

4 Faculty of Medicine, University of Southampton, Southampton, UK

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Molecular Cytogenetics 2013, 6:39  doi:10.1186/1755-8166-6-39

Published: 20 September 2013


ETV6-ABL1 is a rare gene fusion with oncogenic properties, reported so far in 28 patients presenting a variety of haematological malignancies associated with clinical outcome, including chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and chronic myeloproliferative neoplasm (cMPN). Here we report on a 46-year-old female who presented with Philadelphia negative CML, positive for the ETV6-ABL1 fusion. Whole genome screening carried out with oligonucleotide arrays showed a subtle loss at 12p13 and cryptic imbalances within the 9q34.3 region in a highly unstable genome. FISH mapping with custom BAC probes identified two breakpoints 5 Mb apart within the 9q34 region, together with a break at 12p13. While FISH with commercial BCR-ABL1 probes failed to detect any ABL1 changes, the ETV6 break-apart probe conclusively identified the ETV6-ABL1 fusion thus determining the probe‚Äôs role as the primary diagnostic FISH test for this chimeric oncogene. In addition, we confirm the association of the ETV6-ABL1 fusion with imatinib resistance reported so far in three other patients, while recording excellent response to the 2nd generation tyrosine kinase inhibitor (TKI) nilotinib. In summary, we highlight the value of ETV6 FISH as a diagnostic test and the therapy resistance of ETV6-ABL1 positive disorders to imatinib.

ETV6-ABL1; Atypical CML; Nilotinib; Resistance to imatinib