Blood  1990 Jan 15;75(2):453-7 

Alteration of N-ras gene mutation after relapse in acute lymphoblastic leukemia.

Terada N, Miyoshi J, Kawa-Ha K, Sasai H, Orita S, Yumura-Yagi K, Hara J,
Fujinami A, Kakunaga T.

Department of Oncogene Research, Osaka University, Japan.

We investigated N-ras activation in childhood acute lymphoblastic leukemia
(dALL) by the polymerase chain reaction (PCR) and the oligonucleotide
hybridization method. The frequency of point-mutation of the N-ras gene was not
high (2 of 15), and one positive case who relapsed was analyzed in detail.
Although N-ras gene activation was detected at both onset and relapse, the
mutation sites were different. At onset, Gly (GGT) was changed to Ser (AGT) at
codon 12, and at relapse, Gly (GGT) to Asp (GAT) was observed at the same codon.
In addition, the DNA at relapse showed a remarkably higher transforming activity
than the DNA at onset on two independent recipient cell lines. The identical
cell surface phenotype and the same rearrangement patterns of both the
immunoglobulin (Ig) heavy chain and T-cell receptor (TCR) gamma chain genes
indicated that the leukemic cells at onset and those at relapse were derived
from the same precursor cell. Therefore, this case supports the concept that ras
activation is not the event initiating leukemogenesis, but may be involved in
leukemic progression.

PMID: 1967219 [PubMed - indexed for MEDLINE]