Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia.
We have screened mutations of the N-ras gene at codons 12, 13, and 61 in leukemia cells obtained from 100 patients with acute myeloid leukemia (AML), and found mutated N-ras alleles in 9 patients. We further analyzed the polyclonality of multiple N-ras gene mutations in 4 AML patients. One patient, who had the monoclonal karyotype, t(11;17), had two types of double missense mutations at codons 13 and 61 in the same allele. Each of the remaining three patients, one of whom had t(15;17) with a monoclonal rearrangement of the retinoic acid receptor alpha and PML genes, carried two missense mutations in a relatively small population of leukemia cells. We have demonstrated that multiple clonality of the N-ras gene is occasionally observed in leukemia with a monoclonal karyotype. These findings indicate that the N-ras mutations may not always be characterized simply by an accumulative process and that the activated N-ras gene alone is not sufficient to cause leukemia.
Department of Internal Medicine, Nagoya University Branch Hospital.
K
K
Kubo
T
T
Naoe
H
H
Kiyoi
H
H
Fukutani
Y
Y
Kato
T
T
Oguri
S
S
Yamamori
Y
Y
Akatsuka
Y
Y
Kodera
R
R
Ohno
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics; D007948:Leukemia, Monocytic, Acute / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*
D003062:Codon; D004273:DNA, Neoplasm