title: Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia with IKZF1 deletion.
abstract: Activating tyrosine kinase mutations or cytokine receptor signalling alterations have attracted attention as therapeutic targets for high-risk paediatric acute lymphoblastic leukaemia (ALL). We identified two novel kinase fusions, OFD1-JAK2 and NCOR1-LYN, in paediatric ALL patients with IKZF1 deletion, by mRNA sequencing. The patient with CSF2RA-CRLF2 also harboured IGH-EPOR. All these patients had high-risk features, such as high initial white blood cell counts and initial poor response to prednisolone. The functional analysis of these novel fusions is on-going to determine whether these genetic alterations can be targeted by drugs.
authors.affiliation: Department of Paediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Yano
authors.affiliation: Department of Paediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.|Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Division of Paediatrics, Fukuchiyama City Hospital, Fukuchiyama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Asai
authors.affiliation: Department of Paediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Mie University, Tsu, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Deguchi
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Osaka University, Osaka, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hashii
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, University Hospital of Occupational and Environmental Health, Fukuoka, Japan.
authors.forename: Yu-ko
authors.initials: YK
authors.lastname: Honda
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Hematology/Oncology, Hyogo Prefectural Children's Hospital, Kobe, Japan.
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Hasegawa
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sasahara
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Hematology/Oncology, Hyogo Prefectural Children's Hospital, Kobe, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Nara Medical University Hospital, Kashihara, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Mie University, Tsu, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hori
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Yumura Clinic, Osaka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yumura-Yagi
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Osaka City General Hospital, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, Okayama University, Okayama, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Oda
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatrics, National Hospital Organization Nagoya Medical Center, Clinical Resarch Center, Nagoya, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.|Department of Paediatric Hematology/Oncology, Miyagi Children's Hospital, Sendai, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
mesh_terms: D002648:Child; D005260:Female; D017353:Gene Deletion; D050939:Gene Fusion / Q000235:genetics*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D017423:Sequence Analysis, RNA; D019061:src-Family Kinases / Q000235:genetics
chemical_list: C498762:CRLF2 protein, human; C521678:CSF2RA protein, human; C497239:IKZF1 protein, human; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; C115130:OFD1 protein, human; D011506:Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D051740:Ikaros Transcription Factor; D053614:Janus Kinase 2; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases
keywords: IKZF1; Ph-like ALL; kinase fusion; paediatric ALL