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

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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.

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Acknowledgments

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.”

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Correspondence to Carlos Besses.

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Martínez-Avilés, L., Besses, C., Álvarez-Larrán, A. et al. TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2- and MPL-negative myeloproliferative neoplasms. Ann Hematol 91, 533–541 (2012). https://doi.org/10.1007/s00277-011-1330-0

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