Recurrent ETNK1 mutations in atypical chronic myeloid leukemia

Carlo B. Gambacorti-Passerini, Carla Donadoni, Andrea Parmiani, Alessandra Pirola, Sara Redaelli, Giovanni Signore, Vincenzo Piazza, Luca Malcovati, Diletta Fontana, Roberta Spinelli, Vera Magistroni, Giuseppe Gaipa, Marco Peronaci, Alessandro Morotti, Cristina Panuzzo, Giuseppe Saglio, Emilio Usala, Dong Wook Kim, Delphine Rea, Konstantinos ZervakisNora Viniou, Argiris Symeonidis, Heiko Becker, Jacqueline Boultwood, Leonardo Campiotti, Matteo Carrabba, Elena Elli, Graham R. Bignell, Elli Papaemmanuil, Peter J. Campbell, Mario Cazzola, Rocco Piazza

Research output: Contribution to journalArticlepeer-review


Despite the recent identification of recurrent SETBP1 mutations in atypical chronic myeloid leukemia (aCML), a complete description of the somatic lesions responsible for the onset of this disorder is still lacking. To find additional somatic abnormalities in aCML, we performed whole-exome sequencing on 15 aCML cases. In 2 cases (13.3%), we identified somatic missense mutations in the ETNK1 gene. Targeted resequencing on 515 hematological clonal disorders revealed the presence of ETNK1 variants in 6 (8.8%) of 68 aCML and 2 (2.6%) of 77 chronic myelomonocytic leukemia samples. These mutations clustered in a small region of the kinase domain, encoding for H243Y and N244S (1/8 H243Y; 7/8 N244S). They were all heterozygous and present in the dominant clone. The intracellular phosphoethanolamine/phosphocholine ratio was, on average, 5.2-fold lower in ETNK1-mutated samples ( P <.05). Similar results were obtained using myeloid TF1 cells transduced with ETNK1 wild type, ETNK1-N244S, and ETNK1-H243Y, where the intracellular phosphoethanolamine/phosphocholine ratio was significantly lower in ETNK1-N244S (0.76 ± 0.07) and ETNK1-H243Y (0.37 ± 0.02) than in ETNK1-WT (1.37 ± 0.32; P = .01 and P = .0008, respectively), suggesting that ETNK1 mutations may inhibit the catalytic activity of the enzyme. In summary, our study shows for the first time the evidence of recurrent somatic ETNK1 mutations in the context of myeloproliferative/myelodysplastic disorders.

Original languageEnglish
Pages (from-to)499-503
Number of pages5
Issue number3
Publication statusPublished - Jan 15 2015

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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