Constitutional abnormalities of IDH1 combined with secondary mutations predispose a patient with Maffucci syndrome to acute lymphoblastic leukemia
Corresponding Author
Shinsuke Hirabayashi
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan
Correspondence
Shinsuke Hirabayashi, Department of Pediatrics, St. Luke's International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo 1048560, Japan.
Email: [email protected]
Search for more papers by this authorMasafumi Seki
Department of Pediatrics, University of Tokyo, Tokyo, Japan
Search for more papers by this authorDaisuke Hasegawa
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan
Search for more papers by this authorMotohiro Kato
Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorNobuyuki Hyakuna
Center of Bone Marrow Transplantation, Ryukyu University Hospital, Okinawa, Japan
Search for more papers by this authorTakuya Shuo
Institute for Medical Innovation, St. Luke's International University, Tokyo, Japan
Search for more papers by this authorShunsuke Kimura
Department of Pediatrics, University of Tokyo, Tokyo, Japan
Search for more papers by this authorKenichi Yoshida
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorKeisuke Kataoka
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorYoichi Fujii
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorYuichi Shiraishi
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorKenichi Chiba
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorHiroko Tanaka
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorNobutaka Kiyokawa
Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
Search for more papers by this authorSatoru Miyano
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorSeishi Ogawa
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorJunko Takita
Department of Pediatrics, University of Tokyo, Tokyo, Japan
Search for more papers by this authorAtsushi Manabe
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Shinsuke Hirabayashi
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan
Correspondence
Shinsuke Hirabayashi, Department of Pediatrics, St. Luke's International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo 1048560, Japan.
Email: [email protected]
Search for more papers by this authorMasafumi Seki
Department of Pediatrics, University of Tokyo, Tokyo, Japan
Search for more papers by this authorDaisuke Hasegawa
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan
Search for more papers by this authorMotohiro Kato
Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorNobuyuki Hyakuna
Center of Bone Marrow Transplantation, Ryukyu University Hospital, Okinawa, Japan
Search for more papers by this authorTakuya Shuo
Institute for Medical Innovation, St. Luke's International University, Tokyo, Japan
Search for more papers by this authorShunsuke Kimura
Department of Pediatrics, University of Tokyo, Tokyo, Japan
Search for more papers by this authorKenichi Yoshida
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorKeisuke Kataoka
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorYoichi Fujii
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorYuichi Shiraishi
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorKenichi Chiba
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorHiroko Tanaka
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorNobutaka Kiyokawa
Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
Search for more papers by this authorSatoru Miyano
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorSeishi Ogawa
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorJunko Takita
Department of Pediatrics, University of Tokyo, Tokyo, Japan
Search for more papers by this authorAtsushi Manabe
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan
Search for more papers by this authorShinsuke Hirabayashi and Masafumi Seki contributed equally to this work.
Abstract
Maffucci syndrome is a nonhereditary disorder caused by somatic mosaic isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations and is characterized by multiple enchondromas along with hemangiomas. Malignant transformation of enchondromas to chondrosarcomas and secondary neoplasms, such as brain tumors or acute myeloid leukemia, are serious complications. A 15-year-old female with Maffucci syndrome developed B-cell precursor acute lymphoblastic leukemia (BCP-ALL). A somatic mutation in IDH1 was detected in hemangioma and leukemic cells. KRAS mutation and deletion of IKZF1 were detected in leukemic cells. Patients with Maffucci syndrome may, therefore, be at risk of BCP-ALL associated with secondary genetic events that affect lymphocyte differentiation.
Supporting Information
| Filename | Description |
|---|---|
| pbc26647-sup-0001-FigureS1.docx2.5 MB | Supplementary Material S1. Details of samples, direct sequencing, whole-exome sequencing and SNP array analysis. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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