Analysis of mutations of neurofibromatosis type 1 gene and N-ras gene in acute myelogenous leukemia.
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.
Lee
Y Y
YY
Department of Internal Medicine, Han Yang University Hospital, Seoul, Korea.
Kim
W S
WS
Bang
Y J
YJ
Jung
C W
CW
Park
S
S
Yoon
W J
WJ
Cho
K S
KS
Kim
I S
IS
Jung
T J
TJ
Choi
I Y
IY
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D003062:Codon / Q000235:genetics; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D005260:Female; D016514:Genes, Neurofibromatosis 1; D011905:Genes, ras; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012016:Reference Values
D003062:Codon; D017931:DNA Primers; D004273:DNA, Neoplasm