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Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia.
Togasaki, E; Takeda, J; Yoshida, K; Shiozawa, Y; Takeuchi, M; Oshima, M; Saraya, A; Iwama, A; Yokote, K; Sakaida, E; Hirase, C; Takeshita, A; Imai, K; Okumura, H; Morishita, Y; Usui, N; Takahashi, N; Fujisawa, S; Shiraishi, Y; Chiba, K; Tanaka, H; Kiyoi, H; Ohnishi, K; Ohtake, S; Asou, N; Kobayashi, Y; Miyazaki, Y; Miyano, S; Ogawa, S; Matsumura, I; Nakaseko, C; Naoe, T.
Afiliación
  • Togasaki E; Department of Hematology, Chiba University Hospital, Chiba, Japan.
  • Takeda J; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Yoshida K; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Shiozawa Y; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Takeuchi M; Department of Hematology, Chiba University Hospital, Chiba, Japan.
  • Oshima M; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Saraya A; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Iwama A; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Yokote K; Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Sakaida E; Department of Hematology, Chiba University Hospital, Chiba, Japan.
  • Hirase C; Department of Hematology and Rheumatology, Faculty of Medicine, Kinki University, Osaka, Japan.
  • Takeshita A; Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  • Imai K; Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
  • Okumura H; Department of Internal Medicine, Toyama Prefectural Central Hospital, Toyama, Japan.
  • Morishita Y; Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.
  • Usui N; Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan.
  • Takahashi N; Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.
  • Fujisawa S; Department of Hematology, Yokohama City University Medical Center, Yokohama, Japan.
  • Shiraishi Y; Laboratory of DNA Information Analysis, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Chiba K; Laboratory of DNA Information Analysis, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Tanaka H; Laboratory of DNA Information Analysis, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Kiyoi H; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Ohnishi K; Japanese Red Cross Aichi Blood Center, Seto, Japan.
  • Ohtake S; Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
  • Asou N; Department of Hemato-Oncology, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan.
  • Kobayashi Y; Division of Hematology, National Cancer Center Hospital, Tokyo, Japan.
  • Miyazaki Y; Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Miyano S; Laboratory of DNA Information Analysis, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Ogawa S; Laboratory of Sequence Analysis, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Matsumura I; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Nakaseko C; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Naoe T; Department of Hematology, Chiba University Hospital, Chiba, Japan.
Blood Cancer J ; 7(4): e559, 2017 04 28.
Article en En | MEDLINE | ID: mdl-28452984
Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17). Age, hemoglobin concentration and white blood cell counts were correlated with the number of mutations. Patients with mutations ⩾6 showed higher rate of achieving major molecular response than those<6 (P=0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were significantly enriched with cell signaling and cell division pathways. Furthermore, DNA copy number analysis showed that 2 of 24 patients had uniparental disomy of chromosome 1p or 3q, which disappeared major molecular response was achieved. These mutations may play significant roles in CML pathogenesis in addition to the strong driver mutation BCR-ABL1.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Leucemia Mielógena Crónica BCR-ABL Positiva / Proteínas Proto-Oncogénicas / Dioxigenasas / Proteínas de Unión al ADN / Histona Demetilasas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Blood Cancer J Año: 2017 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Leucemia Mielógena Crónica BCR-ABL Positiva / Proteínas Proto-Oncogénicas / Dioxigenasas / Proteínas de Unión al ADN / Histona Demetilasas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Blood Cancer J Año: 2017 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos