Neurofibromatosis type 1 (NF1) gene is a tumor suppressor gene, and the NF1 gene 
product, neurofibromin, can downregulate the N-ras gene. Because the N-ras gene 
is often mutated in acute myelogenous leukemia (AML), we wondered if the NF1 
gene might be mutated in those AML samples not having N-ras mutations. We 
investigated the mutational status of the N-ras gene and the FLR exon of codons 
1371-1423 of the open reading frame of the full-length NF1 cDNA, which has a 
strong homology with the mammalian ras GTPase-activating protein (GAP), 
especially for a stretch of three consecutive amino acids (F, L, R), by 
single-strand conformation polymorphism analysis and direct sequencing in 
samples from patients with AML. Of 48 AML patients, 10 (21%) had point 
(missense) mutations of the N-ras gene involving codons 12, 13 and 61. However, 
mutations in the FLR exon of the NF1 gene were not detected in any of the AML 
samples. We also examined the difference of clinical response to induction 
therapy between AML patients with and without N-ras mutation. A significantly 
lower rate of complete remission was noted in individuals with N-ras gene 
mutations. These results suggest that mutation of the NF1 gene, at least in the 
FLR exon, is very rare in AML and the NF1 gene probably is not a functional 
complement of the N-ras gene mutation. The presence of N-ras gene mutation may 
be associated with a lower clinical response to antileukemic therapy.