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  • Li, Jian FengShanghai Jiao Tong University,Ruijin Hospital (author)

Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-11-28
  • Proceedings of the National Academy of Sciences,2018

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:26dd769e-7441-41b5-8b35-a9ee3b58942e
  • https://lup.lub.lu.se/record/26dd769e-7441-41b5-8b35-a9ee3b58942eURI
  • https://doi.org/10.1073/pnas.1814397115DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223 BCP ALL cases using RNA sequencing. Fourteen BCP ALL gene expression subgroups (G1 to G14) were identified. Apart from extending eight previously described subgroups (G1 to G8 associated with MEF2D fusions, TCF3–PBX1 fusions, ETV6–RUNX1–positive/ETV6–RUNX1–like, DUX4 fusions, ZNF384 fusions, BCR–ABL1/Ph–like, high hyperdiploidy, and KMT2A fusions), we defined six additional gene expression subgroups: G9 was associated with both PAX5 and CRLF2 fusions; G10 and G11 with mutations in PAX5 (p.P80R) and IKZF1 (p.N159Y), respectively; G12 with IGH–CEBPE fusion and mutations in ZEB2 (p.H1038R); and G13 and G14 with TCF3/4–HLF and NUTM1 fusions, respectively. In pediatric BCP ALL, subgroups G2 to G5 and G7 (51 to 65/67 chromosomes) were associated with low-risk, G7 (with ≤50 chromosomes) and G9 were intermediate-risk, whereas G1, G6, and G8 were defined as high-risk subgroups. In adult BCP ALL, G1, G2, G6, and G8 were associated with high risk, while G4, G5, and G7 had relatively favorable outcomes. This large-scale transcriptome sequence analysis of BCP ALL revealed distinct molecular subgroups that reflect discrete pathways of BCP ALL, informing disease classification and prognostic stratification. The combined results strongly advocate that RNA sequencing be introduced into the clinical diagnostic workup of BCP ALL. four decades, most of the recurring chromosomal abnormalities, including aneuploidy, chromosomal rearrangements/gene fusions (e.g., ETV6–RUNX1, BCR–ABL1, and TCF3–PBX1), and rearrangements of KMT2A (previously MLL), were identified by.

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  • Dai, Yu TingShanghai Jiao Tong University,Ruijin Hospital (author)
  • Lilljebjörn, HenrikLund University,Lunds universitet,Translationella genomiska och funktionella studier av leukemi,Forskargrupper vid Lunds universitet,Translational Genomic and Functional Studies of Leukemia,Lund University Research Groups(Swepub:lu)tmb-hli (author)
  • Shen, Shu HongShanghai Jiao Tong University,Shanghai Children’s Medical Center (author)
  • Cui, Bo WenShanghai Jiao Tong University,Ruijin Hospital (author)
  • Bai, LingRuijin Hospital,Shanghai Jiao Tong University (author)
  • Liu, Yuan FangShanghai Jiao Tong University,Ruijin Hospital (author)
  • Qian, Mao XiangSt Jude Children´s Research Hospital, Memphis (author)
  • Kubota, YasuoUniversity of Tokyo (author)
  • Kiyoi, HitoshiNagoya University (author)
  • Matsumura, ItaruKindai University (author)
  • Miyazaki, YasushiNagasaki University (author)
  • Olsson, LindaLund University,Lunds universitet,Genetiska och epigenetiska studier av barnleukemi,Forskargrupper vid Lunds universitet,Genetic and epigenetic studies of pediatric leukemia,Lund University Research Groups(Swepub:lu)med-ldo (author)
  • Tan, Ah MoyKK Women’s and Children’s Hospital (author)
  • Ariffin, HanyUniversity of Malaya (author)
  • Chen, JingShanghai Children’s Medical Center,Shanghai Jiao Tong University (author)
  • Takita, JunkoKyoto University (author)
  • Yasuda, TakahikoNational Hospital Organization, Japan (author)
  • Mano, HiroyukiNational Cancer Center Research Institute, Japan (author)
  • Johansson, BertilLund University,Lunds universitet,Genetiska och epigenetiska studier av barnleukemi,Forskargrupper vid Lunds universitet,Genetic and epigenetic studies of pediatric leukemia,Lund University Research Groups,Regional Laboratories Region Skåne(Swepub:lu)kgen-bjo (author)
  • Yang, Jun J.St Jude Children´s Research Hospital, Memphis (author)
  • Yeoh, Allen Eng JuhNational University of Singapore (author)
  • Hayakawa, FumihikoNagoya University (author)
  • Chen, ZhuShanghai Jiao Tong University,Ruijin Hospital (author)
  • Pui, Ching HonSt Jude Children´s Research Hospital, Memphis (author)
  • Fioretos, ThoasLund University,Lunds universitet,Translationella genomiska och funktionella studier av leukemi,Forskargrupper vid Lunds universitet,Translational Genomic and Functional Studies of Leukemia,Lund University Research Groups,Regional Laboratories Region Skåne(Swepub:lu)kgen-tfi (author)
  • Chen, Sai JuanRuijin Hospital,Shanghai Jiao Tong University (author)
  • Huang, Jin YanRuijin Hospital,Shanghai Jiao Tong University (author)
  • Shanghai Jiao Tong UniversityRuijin Hospital (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences115:50, s. 11711-117200027-8424
  • In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences115:50, s. 11711-117201091-6490

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