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 Xu; Nobuhiro Nishio; Makito Tanaka; Asahito Hama; Kenichi Koike; Seiji Kojima

doi:10.1182/blood-2012-02-406090

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 journal › Article › peer-review

25 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	1485-1488
Number of pages	4
Journal	Blood
Volume	120
Issue number	7
DOIs	https://doi.org/10.1182/blood-2012-02-406090
Publication status	Published - 16-08-2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Immunology
Hematology
Cell Biology

Access to Document

10.1182/blood-2012-02-406090

Cite this

Doisaki, S., Muramatsu, H., Shimada, A., Takahashi, Y., Mori-Ezaki, M., Sato, M., Kawaguchi, H., Kinoshita, A., Sotomatsu, M., Hayashi, Y., Furukawa-Hibi, Y., Yamada, K., Hoshino, H., Kiyoi, H., Yoshida, N., Sakaguchi, H., Narita, A., Wang, X., Ismael, O., ... Kojima, S. (2012). Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia. Blood, 120(7), 1485-1488. https://doi.org/10.1182/blood-2012-02-406090

@article{a9a03eff202844ad968ac3ec5a58d4e1,

title = "Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia",

abstract = "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.",

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

year = "2012",

month = aug,

day = "16",

doi = "10.1182/blood-2012-02-406090",

language = "English",

volume = "120",

pages = "1485--1488",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier B.V.",

number = "7",

}

Doisaki, S, Muramatsu, H, Shimada, A, Takahashi, Y, Mori-Ezaki, M, Sato, M, Kawaguchi, H, Kinoshita, A, Sotomatsu, M, Hayashi, Y, Furukawa-Hibi, Y, Yamada, K, Hoshino, H, Kiyoi, H, Yoshida, N, Sakaguchi, H, Narita, A, Wang, X, Ismael, O, Xu, Y, Nishio, N, Tanaka, M, Hama, A, Koike, K & Kojima, S 2012, 'Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia', Blood, vol. 120, no. 7, pp. 1485-1488. https://doi.org/10.1182/blood-2012-02-406090

TY - JOUR

T1 - Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia

AU - Doisaki, Sayoko

AU - Muramatsu, Hideki

AU - Shimada, Akira

AU - Takahashi, Yoshiyuki

AU - Mori-Ezaki, Makiko

AU - Sato, Masanori

AU - Kawaguchi, Hiroyuki

AU - Kinoshita, Akitoshi

AU - Sotomatsu, Manabu

AU - Hayashi, Yasuhide

AU - Furukawa-Hibi, Yoko

AU - Yamada, Kiyofumi

AU - Hoshino, Hideaki

AU - Kiyoi, Hitoshi

AU - Yoshida, Nao

AU - Sakaguchi, Hirotoshi

AU - Narita, Atsushi

AU - Wang, Xinan

AU - Ismael, Olfat

AU - Xu, Yinyan

AU - Nishio, Nobuhiro

AU - Tanaka, Makito

AU - Hama, Asahito

AU - Koike, Kenichi

AU - Kojima, Seiji

PY - 2012/8/16

Y1 - 2012/8/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84865155361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865155361&partnerID=8YFLogxK

U2 - 10.1182/blood-2012-02-406090

DO - 10.1182/blood-2012-02-406090

M3 - Article

C2 - 22753870

AN - SCOPUS:84865155361

SN - 0006-4971

VL - 120

SP - 1485

EP - 1488

JO - Blood

JF - Blood

IS - 7

ER -

Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this