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Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms
  1. C S Chim1,
  2. T S Wan2,
  3. T K Fung1,
  4. K F Wong3
  1. 1Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong
  2. 2Department Pathology, Queen Mary Hospital, University of Hong Kong, Hong Kong
  3. 3Department of Pathology, Queen Elizabeth Hospital, Hong Kong
  1. Correspondence to Dr C S Chim, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, 852, Hong Kong; jcschim{at}


A loss-of-function mutation of TET2, CBL and CEBPA has been implicated in the pathogenesis or leukaemic transformation of myeloproliferative neoplasm. As tumour suppressor genes may potentially be inactivated by promoter hypermethylation, the authors studied the methylation status of these genes in three cell lines and diagnostic marrow samples from 45 patients with myeloproliferative neoplasm (MPN) (essential thrombocythaemia, N=34; polycythaemia vera, N=7 and primary myelofibrosis, N=4) by methylation-specific PCR. TET2 was heterozygously methylated in MEG-01 and K562 but completely unmethylated in HEL. On the other hand, both CBL and CEBPA were completely unmethylated in all three cell lines. In the primary marrow samples, methylation of TET2 occurred in two (5.9%) patients with essential thrombocythaemia (4.4% of all patients), both without JAK2 V617 mutation, but not in polycythaemia vera or primary myelofibrosis. There was no association between TET2 methylation with the type of MPN (p=0.713). Hypermethylation of CBL or CEBPA was not detected in any patients. In summary, methylation of TET2, CBL and CEBPA is infrequent in MPN at diagnosis. The role of methylation of these genes at the time of leukaemic transformation warrants further study.

  • CBL
  • TET2
  • gene methylation
  • myeloproliferative neoplasm
  • bone marrow
  • cancer genetics
  • myeloproliferative disease

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  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the Institutional Review Board of Queen Mary Hospital.

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