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.

journal_name

Blood

journal_title

Blood

authors

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

doi

10.1182/blood-2012-02-406090

subject

Has Abstract

pub_date

2012-08-16 00:00:00

pages

1485-8

issue

7

eissn

0006-4971

issn

1528-0020

pii

blood-2012-02-406090

journal_volume

120

pub_type

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