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

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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.


  • Jian Feng Li
  • Yu Ting Dai
  • Shu Hong Shen
  • Bo Wen Cui
  • Ling Bai
  • Yuan Fang Liu
  • Mao Xiang Qian
  • Yasuo Kubota
  • Hitoshi Kiyoi
  • Itaru Matsumura
  • Yasushi Miyazaki
  • Ah Moy Tan
  • Hany Ariffin
  • Jing Chen
  • Junko Takita
  • Takahiko Yasuda
  • Hiroyuki Mano
  • Jun J. Yang
  • Allen Eng Juh Yeoh
  • Fumihiko Hayakawa
  • Zhu Chen
  • Ching Hon Pui
  • Sai Juan Chen
  • Jin Yan Huang
External organisations
  • Shanghai Jiao Tong University
  • St Jude Children´s Research Hospital, Memphis
  • University of Tokyo
  • Nagoya University
  • Kindai University
  • Nagasaki University
  • KK Women’s and Children’s Hospital
  • University of Malaya
  • Kyoto University
  • National Hospital Organization, Japan
  • National Cancer Center Research Institute, Japan
  • Regional Laboratories Region Skåne
  • National University of Singapore
  • Ruijin Hospital
  • Shanghai Children’s Medical Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • BCP ALL, Gene fusion, Gene mutation, RNA-seq, Subtypes
Original languageEnglish
Pages (from-to)E11711-E11720
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
Publication statusPublished - 2018
Publication categoryResearch