Somatic mosaic mutations of IDH1 and NPM1 associated with cup-like acute myeloid leukemia in a patient with Maffucci syndrome.
Maffucci syndrome is a nonhereditary congenital disorder characterized by multiple enchondromas and with soft-tissue hemangiomas. Somatic mutations of the isocitrate dehydrogenase (IDH) gene have been detected in enchondroma and hemangioma tissue from patients with Maffucci syndrome. The rate of malignant transformation in Maffucci syndrome is high, with enchondromas transforming into chondrosarcomas and the development of secondary neoplasms, including pancreatic and hepatic adenocarcinoma, mesenchymal ovarian tumors, and brain tumors such as glioma. However, hematopoietic malignancies arising in Maffucci syndrome are rare. We report a 7-year-old girl with Maffucci syndrome in whom acute myeloid leukemia (AML) with cup-like nuclear invagination developed. Both leukemic cells and hemangioma had the same gene mutations: an insertion frameshift c.863_864insTCTG (p.W288 fs) in the nucleophosmin (NPM1) gene and a missense mutation c.392_395GTCG > CTCT (p.G131_R132 > AL) in the IDH1 gene. However, buccal mucosa cells and peripheral blood mononuclear cells harvested after two cycles of chemotherapy showed wild-type genotypes. These results suggest that the multiple somatic mutations of the IDH1 and NPM1 genes in hemangioblasts are related to the development of cup-like AML associated with Maffucci syndrome. However, further studies are needed to identify additional molecular events in AML but not in hemangioma.
Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan. makiyama@jikei.ac.jp.|Research Center for Medical Science, Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan. makiyama@jikei.ac.jp.
Masaharu
M
Akiyama
Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Masayoshi
M
Yamaoka
Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Yoko
Y
Mikami-Terao
Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Wataru
W
Ohyama
Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Kentaro
K
Yokoi
Department of Adult Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan.
Yasuhiro
Y
Arakawa
Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Junko
J
Takita
Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.
Hideaki
H
Suzuki
Research Center for Medical Science, Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan.
Hisashi
H
Yamada
D002648:Child; D004687:Enchondromatosis / Q000150:complications* / Q000235:genetics*; D056726:Genetic Association Studies; D055018:Hemangioblasts; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
Acute myeloid leukemia; Hemangioma; Isocitrate dehydrogenase; Maffucci syndrome; Nucleophosmin