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Mutational profiling in suspected triple-negative essential thrombocythaemia using targeted next-generation sequencing in a real-world cohort
  1. Olga Michail1,
  2. Patrick McCallion1,
  3. Julie McGimpsey1,
  4. Andrew Hindley1,
  5. Graeme Greenfield1,
  6. Roisin McAllister1,
  7. John Feerick1,
  8. Claire Arnold1,
  9. Nick Cross2,
  10. Robert Cuthbert1,
  11. Mary F McMullin3,
  12. Mark A Catherwood1
  1. 1 Department of Clinical Haematology, Belfast Health and Social Care Trust, Belfast, UK
  2. 2 Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK
  3. 3 Centre for Medical Education, Queen’s University Belfast, Belfast, UK
  1. Correspondence to Dr Mark A Catherwood, Haematology, Belfast Health and Social Care Trust, Belfast BT9 7AB, Belfast, UK; mark.catherwood{at}belfasttrust.hscni.net

Abstract

Essential thrombocythaemia (ET) is driven by somatic mutations involving the JAK2, CALR and MPL genes. Approximately 10% of patients lack driver mutations and are referred as ‘triple-negative’ ET (TN-ET). The diagnosis of TN-ET, however, relies on bone marrow examination that is not always performed in routine practice, and thus in the real-world setting, there are a group of cases with suspected TN-myeloproliferativeneoplasm.

In this real-world cohort, patients with suspected TN-ET were initially rescreened for JAK2, CALR and MPL and then targeted next-generation sequencing (NGS) was applied.

The 35 patients with suspected TN-ET had a median age at diagnosis of 43 years (range 16–79) and a follow-up of 10 years (range 2–28). The median platelet count was 758×109/L (range 479–2903). Thrombosis prior to and following diagnosis was noted in 20% and 17% of patients. Six patients were JAK2V617F and two patients were CALR positive on repeat screening. NGS results showed that 24 of 27 patients harboured no mutations. Four mutations were noted in three patients.

There was no evidence of clonality for the majority of patients with suspected TN-ET with targeted NGS analysis. Detection of driver mutations in those who were previously screened suggests that regular rescreening is required. This study also questions the diagnosis of TN-ET without the existence of a clonal marker.

  • myeloproliferative disorders
  • molecular biology
  • diagnosis

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Footnotes

  • Handling editor Tahir S Pillay.

  • Correction notice This article has been corrected since it was published Online First. Roisin McAllister has been added as an author of the paper.

  • Contributors MAC and OM wrote the manuscript and prepared all figures. CA, NC, MFM, PM, AH, JF, GG, JM and RM contributed to the writing of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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