例如:"lncRNA", "apoptosis", "WRKY"

Recurrent ETNK1 mutations in atypical chronic myeloid leukemia.

Blood. 2015 Jan 15;125(3):499-503. Epub 2014 Oct 24
Carlo B Gambacorti-Passerini 1 , Carla Donadoni 2 , Andrea Parmiani 2 , Alessandra Pirola 2 , Sara Redaelli 2 , Giovanni Signore 3 , Vincenzo Piazza 3 , Luca Malcovati 4 , Diletta Fontana 2 , Roberta Spinelli 2 , Vera Magistroni 2 , Giuseppe Gaipa 5 , Marco Peronaci 2 , Alessandro Morotti 6 , Cristina Panuzzo 6 , Giuseppe Saglio 6 , Emilio Usala 7 , Dong-Wook Kim 8 , Delphine Rea 9 , Konstantinos Zervakis 10 , Nora Viniou 10 , Argiris Symeonidis 11 , Heiko Becker 12 , Jacqueline Boultwood 13 , Leonardo Campiotti 14 , Matteo Carrabba 15 , Elena Elli 16 , Graham R Bignell 17 , Elli Papaemmanuil 17 , Peter J Campbell 17 , Mario Cazzola 4 , Rocco Piazza 2
Carlo B Gambacorti-Passerini 1 , Carla Donadoni 2 , Andrea Parmiani 2 , Alessandra Pirola 2 , Sara Redaelli 2 , Giovanni Signore 3 , Vincenzo Piazza 3 , Luca Malcovati 4 , Diletta Fontana 2 , Roberta Spinelli 2 , Vera Magistroni 2 , Giuseppe Gaipa 5 , Marco Peronaci 2 , Alessandro Morotti 6 , Cristina Panuzzo 6 , Giuseppe Saglio 6 , Emilio Usala 7 , Dong-Wook Kim 8 , Delphine Rea 9 , Konstantinos Zervakis 10 , Nora Viniou 10 , Argiris Symeonidis 11 , Heiko Becker 12 , Jacqueline Boultwood 13 , Leonardo Campiotti 14 , Matteo Carrabba 15 , Elena Elli 16 , Graham R Bignell 17 , Elli Papaemmanuil 17 , Peter J Campbell 17 , Mario Cazzola 4 , Rocco Piazza 2
+ et al

[No authors listed]

Author information
  • 1 Department of Health Sciences, University of Milano-Bicocca, Monza, Italy; Hematology and Clinical Research Unit, San Gerardo Hospital, Monza, Italy;
  • 2 Department of Health Sciences, University of Milano-Bicocca, Monza, Italy;
  • 3 Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Pisa, Italy;
  • 4 Department of Hematology Oncology, Fondazione Istituto di ricovero e cura a carattere scientifico Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Pavia, Italy;
  • 5 Tettamanti Research Center, Pediatric Clinic University of Milano-Bicocca, Monza, Italy;
  • 6 Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Turin, Italy;
  • 7 S.C. di Ematologia e Centro Trapianti di Cellule Staminali Emopoietiche, Dipartimento di Oncologia Medica, Ospedale Oncologico "Armando Businco," Cagliari, Italy;
  • 8 Department of Hematology, Catholic University, Seoul, Korea;
  • 9 Service d'Hématologie adulte, Hôpital Saint-Louis, Paris, France;
  • 10 1st Department of Internal Medicine, Hematology Unit, LAIKON Hospital, National and Kapodistrian University of Athens, Athens, Greece;
  • 11 Hematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, Greece;
  • 12 Universitätsklinikum Freiburg, Innere Medizin I-Hämatologie, Onkologie, und Stammzelltransplantation, Freiburg, Germany;
  • 13 Leukaemia and Lymphoma Research Molecular Hematology Unit, John Radcliffe Hospital, Oxford, United Kingdom;
  • 14 Dipartimento Medicina Clinica e Sperimentale, Università Insubria, Varese, Italy;
  • 15 Ematologia e Trapianto di Midollo, Istituto di ricovero e cura a carattere scientifico, Ospedale San Raffaele, Milano, Italy;
  • 16 Hematology Unit, San Gerardo Hospital, Monza, Italy; and.
  • 17 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.

摘要


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.