Diagenode

Recurrent ETNK1 mutations in atypical chronic myeloid leukemia.


Gambacorti-Passerini CB, Donadoni C, Parmiani A, Pirola A, Redaelli S, Signore G, Piazza V, Malcovati L, Fontana D, Spinelli R, Magistroni V, Gaipa G, Peronaci M, Morotti A, Panuzzo C, Saglio G, Usala E, Kim DW, Rea D, Zervakis K, Viniou N, Symeonidis A,

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.

Tags
DNA shearing
Bioruptor
Bioruptor Plus

Share this article

Published
January, 2015

Source

活动

  • Long-Read Sequencing Meeting 2024
    Uppsala, Sweden
    Oct 21-Oct 23, 2024
  • NextGen Omics 2024
    London, UK
    Oct 23-Oct 25, 2024
  • FEBS 2024
    Budapest, Hungary
    Oct 28-Oct 31, 2024
  • 5th Danube Conference on Epigenetics
    Budapest, Hungary
    Oct 28-Oct 31, 2024
 查看所有活动

 


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy