Double mutations of the N-ras gene in a patient with acute myelomonocytic leukemia.
We report a patient with acute myelomonocytic leukemia (AMMoL) who showed two independent point mutations of the N-ras gene at codons 12 and 13. Longitudinal analysis revealed that one mutation at codon 13 was detectable throughout his disease course and the other at codon 12 emerged as a second mutation 14 months after the diagnosis was made, at the refractory stage. Cloning to vector and subsequent sequencing confirmed that these mutations occurred in different alleles. Chromosome findings showed a simple abnormal karyotype at presentation and further karyotypic aberrations during his disease course, concomitantly with the second mutation of the N-ras gene. These findings revealed a close relationship among the disease progression, karyotypic evolution and a newly-appearing N-ras mutation.
Horiike
S
S
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Misawa
S
S
Kaneko
H
H
Nakai
H
H
Ueda
Y
Y
Nakao
M
M
Hirakawa
K
K
Taniwaki
M
M
Kashima
K
K
D015250:Aclarubicin / Q000008:administration & dosage; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000648:ultrastructure; D003062:Codon / Q000235:genetics; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003630:Daunorubicin / Q000008:administration & dosage; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D017809:Fatal Outcome; D011905:Genes, ras; D005822:Genetic Vectors; D006801:Humans; D007621:Karyotyping; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D017354:Point Mutation; D011239:Prednisolone / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D003062:Codon; D003561:Cytarabine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D015250:Aclarubicin; D004317:Doxorubicin; D011239:Prednisolone; C015019:enocitabine; D008942:Mitoxantrone; D015122:Mercaptopurine; D003630:Daunorubicin