Double mutations of the N-ras gene in a patient with acute myelomonocytic leukemia

• Published in: International journal of hematology Vol. 61; no. 4; p. 205
• Main Authors: Horiike, S, Misawa, S, Kaneko, H, Nakai, H, Ueda, Y, Nakao, M, Hirakawa, K, Taniwaki, M, Kashima, K
• Format: Journal Article
• Language: English
• Published: Japan 01-06-1995
• Subjects: Aclarubicin - administration & dosage; Alleles; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Chromosome Deletion; Chromosomes, Human, Pair 12 - ultrastructure; Chromosomes, Human, Pair 9 - ultrastructure; Codon - genetics; Cytarabine - administration & dosage; Cytarabine - analogs & derivatives; Daunorubicin - administration & dosage; Disease Progression; Doxorubicin - administration & dosage; Etoposide - administration & dosage; Fatal Outcome; Genes, ras; Genetic Vectors; Humans; Karyotyping; Leukemia, Myelomonocytic, Acute - drug therapy; Leukemia, Myelomonocytic, Acute - genetics; Male; Mercaptopurine - administration & dosage; Middle Aged; Mitoxantrone - administration & dosage; Point Mutation; Prednisolone - administration & dosage; Vinblastine - administration & dosage; Vincristine - administration & dosage
• ISSN: 0925-5710
• DOI: 10.1016/0925-5710(95)00366-z

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.