Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia with IKZF1 deletion

Mio Yano; Toshihiko Imamura; Daisuke Asai; Nobutaka Kiyokawa; Kazuhiko Nakabayashi; Kenji Matsumoto; Takao Deguchi; Yoshiko Hashii; Yu-ko Honda; Daiichiro Hasegawa; Yoji Sasahara; Mutsuo Ishii; Yoshiyuki Kosaka; Koji Kato; Midori Shima; Hiroki Hori; Keiko Yumura-Yagi; Junichi Hara; Megumi Oda; Keizo Horibe; Hitoshi Ichikawa; Atsushi Sato

doi:10.1111/bjh.13757

Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia with IKZF1 deletion

Br J Haematol. 2015 Dec;171(5):813-7. doi: 10.1111/bjh.13757. Epub 2015 Sep 25.

Authors

Mio Yano¹, Toshihiko Imamura^{1

2}, Daisuke Asai³, Nobutaka Kiyokawa⁴, Kazuhiko Nakabayashi⁵, Kenji Matsumoto⁶, Takao Deguchi^{2

7}, Yoshiko Hashii^{2

8}, Yu-ko Honda^{2

9}, Daiichiro Hasegawa^{2

10}, Yoji Sasahara^{2

11}, Mutsuo Ishii^{2

12}, Yoshiyuki Kosaka^{2

10}, Koji Kato^{2

13}, Midori Shima^{2

14}, Hiroki Hori^{2

7}, Keiko Yumura-Yagi^{2

15}, Junichi Hara^{2

16}, Megumi Oda^{2

17}, Keizo Horibe^{2

18}, Hitoshi Ichikawa¹⁹, Atsushi Sato^{2

20}

Affiliations

¹ Department of Paediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
² Japan Association of Childhood Leukaemia Study (JACLS), Osaka, Japan.
³ Division of Paediatrics, Fukuchiyama City Hospital, Fukuchiyama, Japan.
⁴ Department of Paediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
⁵ Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
⁶ Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
⁷ Department of Paediatrics, Mie University, Tsu, Japan.
⁸ Department of Paediatrics, Osaka University, Osaka, Japan.
⁹ Department of Paediatrics, University Hospital of Occupational and Environmental Health, Fukuoka, Japan.
¹⁰ Department of Hematology/Oncology, Hyogo Prefectural Children's Hospital, Kobe, Japan.
¹¹ Department of Paediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
¹² Department of Paediatrics, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
¹³ Department of Paediatrics, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
¹⁴ Department of Paediatrics, Nara Medical University Hospital, Kashihara, Japan.
¹⁵ Yumura Clinic, Osaka, Japan.
¹⁶ Department of Paediatrics, Osaka City General Hospital, Osaka, Japan.
¹⁷ Department of Paediatrics, Okayama University, Okayama, Japan.
¹⁸ Department of Paediatrics, National Hospital Organization Nagoya Medical Center, Clinical Resarch Center, Nagoya, Japan.
¹⁹ Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
²⁰ Department of Paediatric Hematology/Oncology, Miyagi Children's Hospital, Sendai, Japan.

PMID: 26404892
DOI: 10.1111/bjh.13757

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.

Keywords: IKZF1; Ph-like ALL; kinase fusion; paediatric ALL.

MeSH terms

Child
Female
Gene Deletion*
Gene Fusion / genetics*
Humans
Ikaros Transcription Factor / genetics
Janus Kinase 2 / genetics
Male
Nuclear Receptor Co-Repressor 1 / genetics
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Proteins / genetics
RNA, Messenger / genetics
Receptors, Cytokine / genetics
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics
Sequence Analysis, RNA
src-Family Kinases / genetics

Substances

CRLF2 protein, human
CSF2RA protein, human
IKZF1 protein, human
NCOR1 protein, human
Nuclear Receptor Co-Repressor 1
OFD1 protein, human
Proteins
RNA, Messenger
Receptors, Cytokine
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Ikaros Transcription Factor
Janus Kinase 2
lyn protein-tyrosine kinase
src-Family Kinases