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Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia.
Seki, Masafumi; Kimura, Shunsuke; Isobe, Tomoya; Yoshida, Kenichi; Ueno, Hiroo; Nakajima-Takagi, Yaeko; Wang, Changshan; Lin, Lin; Kon, Ayana; Suzuki, Hiromichi; Shiozawa, Yusuke; Kataoka, Keisuke; Fujii, Yoichi; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Shimamura, Teppei; Masuda, Kyoko; Kawamoto, Hiroshi; Ohki, Kentaro; Kato, Motohiro; Arakawa, Yuki; Koh, Katsuyoshi; Hanada, Ryoji; Moritake, Hiroshi; Akiyama, Masaharu; Kobayashi, Ryoji; Deguchi, Takao; Hashii, Yoshiko; Imamura, Toshihiko; Sato, Atsushi; Kiyokawa, Nobutaka; Oka, Akira; Hayashi, Yasuhide; Takagi, Masatoshi; Manabe, Atsushi; Ohara, Akira; Horibe, Keizo; Sanada, Masashi; Iwama, Atsushi; Mano, Hiroyuki; Miyano, Satoru; Ogawa, Seishi; Takita, Junko.
  • Seki M; Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Kimura S; Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Isobe T; Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
  • Yoshida K; Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Ueno H; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Nakajima-Takagi Y; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Wang C; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Lin L; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Kon A; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
  • Suzuki H; 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.
  • Kataoka K; Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Fujii Y; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Shiraishi Y; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Chiba K; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Tanaka H; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Shimamura T; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Masuda K; Division of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Kawamoto H; Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • Ohki K; Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • Kato M; Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
  • Arakawa Y; Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
  • Koh K; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
  • Hanada R; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
  • Moritake H; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
  • Akiyama M; Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Kobayashi R; Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
  • Deguchi T; Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan.
  • Hashii Y; Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
  • Imamura T; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Sato A; Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
  • Kiyokawa N; Department of Hematology and Oncology, Miyagi Children's Hospital, Sendai, Japan.
  • Oka A; Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
  • Hayashi Y; Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Takagi M; Gunma Children's Medical Center, Shibukawa, Japan.
  • Manabe A; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
  • Ohara A; Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
  • Horibe K; Department of Pediatrics, Toho University, Tokyo, Japan.
  • Sanada M; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
  • Iwama A; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
  • Mano H; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Miyano S; Department of Cellular Signaling, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Ogawa S; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • Takita J; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nat Genet ; 49(8): 1274-1281, 2017 Aug.
Article en En | MEDLINE | ID: mdl-28671687
ABSTRACT
The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric T-ALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), accounting for 3.9% (7/181) of the examined pediatric T-ALL cases, showed a double-negative (DN; CD4-CD8-) or CD8+ single-positive (SP) phenotype and had uniformly poor overall survival. These cases represent a subset of pediatric T-ALL distinguishable from the known T-ALL subsets in terms of expression of genes involved in T cell precommitment, establishment of T cell identity, and post-ß-selection maturation and with respect to mutational profile. PU.1 fusion proteins retained transcriptional activity and, when constitutively expressed in mouse stem/progenitor cells, induced cell proliferation and resulted in a maturation block. Our findings highlight a unique role of SPI1 fusions in high-risk pediatric T-ALL.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Transactivadores / Proteínas Proto-Oncogénicas / Fusión Génica / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Año: 2017 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Transactivadores / Proteínas Proto-Oncogénicas / Fusión Génica / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Año: 2017 Tipo del documento: Article