Annals of Hematology

, Volume 91, Issue 4, pp 533–541 | Cite as

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

  • Luz Martínez-Avilés
  • Carlos Besses
  • Alberto Álvarez-Larrán
  • Erica Torres
  • Sergi Serrano
  • Beatriz Bellosillo
Original Article


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.


TET2 ASXL1 IDH1 IDH2 c-CBL Mutations 



This work was supported by grants from the Spanish Health Ministry “Fondo de Investigación Sanitaria” EC 07/90791, PI10/01807, Instituto de Salud Carlos III FEDER (RD09/0076/00036), and the “Xarxa de Bancs de Tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC)”. Luz Martínez-Avilés is recipient of a fellowship from the “Comissionat per a Universitats i Recerca del department d’ Innovació, Universitats i Empresa de la Generalitat de Catalunya i del Fons Social Europeu.”

Supplementary material

277_2011_1330_MOESM1_ESM.doc (33 kb)
Supplementary Table 1 (DOC 33 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Luz Martínez-Avilés
    • 1
    • 3
    • 5
  • Carlos Besses
    • 2
    • 5
  • Alberto Álvarez-Larrán
    • 2
    • 5
  • Erica Torres
    • 1
  • Sergi Serrano
    • 1
    • 3
  • Beatriz Bellosillo
    • 1
    • 4
    • 5
  1. 1.Department of PathologyHospital del MarBarcelonaSpain
  2. 2.Department of Clinical HematologyHospital del MarBarcelonaSpain
  3. 3.Universitat Autònoma de Barcelona, IMIM-Hospital del MarBarcelonaSpain
  4. 4.Universitat Pompeu Fabra, IMIM-Hospital del MarBarcelonaSpain
  5. 5.Grup de Recerca Aplicada en Neoplasies Hematològiques, IMIM-Hospital del MarBarcelonaSpain

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