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Mutations of the N-ras gene in juvenile chronic myelogenous leukemia
J Miyauchi, M Asada, M Sasaki, Y Tsunematsu, S Kojima and S Mizutani
Department of Virology, National Children's Medical Research Center, Tokyo,
Japan.
Juvenile chronic myelogenous leukemia (JCML), a myeloproliferative disorder
of childhood, is distinct from adult-type chronic myelogenous leukemia
(CML) and bears resemblance to chronic myelomonocytic leukemia (CMMoL).
Since mutations in the N-ras gene have been found at high frequencies in
CMMoL, but only rarely in CML, we analyzed mutations activating the N-ras
gene in 20 patients with JCML. We used the strategy for analysis of gene
mutations based on in vitro DNA amplification by polymerase chain reaction
(PCR) followed by single- strand conformation polymorphism (SSCP) analysis
and/or direct sequence analysis. Nucleotide sequence analysis showed single
nucleotide substitutions involving codons 12, 13, or 61 in six of 20
patients (30%). Four of six patients with mutations were in chronic phase
and the other two in blast crisis, indicating no apparent correlation with
disease stage. Most of the patients with mutations were in the older age
group with poor prognosis, although one patient in the younger age group
also harbored the mutation. These data suggest that N-ras gene mutations
may be involved in the pathogenesis and/or prognosis of JCML and provide
further evidence that JCML is an entity distinct from CML.
Volume 83,
Issue 8,
pp. 2248-2254,
04/15/1994
Copyright © 1994 by The American Society of Hematology
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