Original Article

Annals of Hematology

, Volume 91, Issue 4, pp 533-541

First online:

TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2- and MPL-negative myeloproliferative neoplasms

  • Luz Martínez-AvilésAffiliated withDepartment of Pathology, Hospital del MarUniversitat Autònoma de Barcelona, IMIM-Hospital del MarGrup de Recerca Aplicada en Neoplasies Hematològiques, IMIM-Hospital del Mar
  • , Carlos BessesAffiliated withDepartment of Clinical Hematology, Hospital del MarGrup de Recerca Aplicada en Neoplasies Hematològiques, IMIM-Hospital del Mar Email author 
  • , Alberto Álvarez-LarránAffiliated withDepartment of Clinical Hematology, Hospital del MarGrup de Recerca Aplicada en Neoplasies Hematològiques, IMIM-Hospital del Mar
  • , Erica TorresAffiliated withDepartment of Pathology, Hospital del Mar
  • , Sergi SerranoAffiliated withDepartment of Pathology, Hospital del MarUniversitat Autònoma de Barcelona, IMIM-Hospital del Mar
  • , Beatriz BellosilloAffiliated withDepartment of Pathology, Hospital del MarUniversitat Pompeu Fabra, IMIM-Hospital del MarGrup de Recerca Aplicada en Neoplasies Hematològiques, IMIM-Hospital del Mar

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Abstract

Mutations in the TET2 and ASXL1 genes have been described in approximately 14% and 8% of patients, respectively, with classic myeloproliferative neoplasms (MPN), but their role as possible new diagnostic molecular markers is still inconclusive. In addition, other genes such as IDH1, IDH2, and c-CBL have also been reported in several myeloid neoplasms. We have studied the mutational status of TET2 (complete coding region), ASXL1 (exon12), IDH1 (R132), IDH2 (R140 and R172), and c-CBL (exons 8 and 9) in 62 MPN patients (52 essential thrombocythemia (ET), five polycythemia vera (PV), and five primary myelofibrosis (PMF)) negative for both JAK2 (V617F and exon 12) and MPL (exon 10) mutations. Pathogenic alterations in the TET2 gene were detected in three out 52 ET cases (4.8%). ASXL1 gene pathogenic mutations were also detected in three cases (two ET and one PMF). One ET patient harbored, simultaneously, one TET2 and one ASXL1 mutations. Mutations in the TET2 and ASXL1 genes showed no association with the JAK2 46/1 haplotype. Analysis of a JAK2V617F-positive cohort of 50 ET patients showed no mutations in either the TET2 or ASXL1 genes. Regarding IDH1, IDH2, and c-CBL genes, no mutations were found in any patient. In conclusion, TET2 and ASXL1 pathogenic mutations are found in 8% of MPN lacking JAK2 and MPL mutations, whereas IDH1, IDH2, and c-CBL mutations are not detected in this subset of patients.

Keywords

TET2 ASXL1 IDH1 IDH2 c-CBL Mutations