Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia

Sayoko Doisaki, Hideki Muramatsu, Akira Shimada, Yoshiyuki Takahashi, Makiko Mori-Ezaki, Masanori Sato, Hiroyuki Kawaguchi, Akitoshi Kinoshita, Manabu Sotomatsu, Yasuhide Hayashi, Yoko Furukawa-Hibi, Kiyofumi Yamada, Hideaki Hoshino, Hitoshi Kiyoi, Nao Yoshida, Hirotoshi Sakaguchi, Atsushi Narita, Xinan Wang, Olfat Ismael, Yinyan XuNobuhiro Nishio, Makito Tanaka, Asahito Hama, Kenichi Koike, Seiji Kojima

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myeloid neoplasm characterized by excessive proliferation of myelomonocytic cells. Somatic mutations in genes involved in GM-CSF signal transduction, such as NRAS, KRAS, PTPN11, NF1, and CBL, have been identified in more than 70% of children with JMML. In the present study, we report 2 patients with somatic mosaicism for oncogenic NRAS mutations (G12D and G12S) associated with the development of JMML. The mutated allele frequencies quantified by pyrosequencing were various and ranged from 3%-50% in BM and other somatic cells (ie, buccal smear cells, hair bulbs, or nails). Both patients experienced spontaneous improvement of clinical symptoms and leukocytosis due to JMML without hematopoietic stem cell transplantation. These patients are the first reported to have somatic mosaicism for oncogenic NRAS mutations. The clinical course of these patients suggests that NRAS mosaicism may be associated with a mild disease phenotype in JMML.

Original languageEnglish
Pages (from-to)1485-1488
Number of pages4
Issue number7
Publication statusPublished - 16-08-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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