DOUBLE MUTATIONS OF THE N-RAS GENE IN A PATIENT WITH ACUTE MYELOMONOCYTIC LEUKEMIA

We report a patient with acute myelomonocytic leukemia (AMMoL) who sho wed 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 eme rged as a second mutation 14 months after the diagnosis was made, at t he refractory stage. Cloning to vector and subsequent sequencing confi rmed that these mutations occurred in different alleles. Chromosome fi ndings showed a simple abnormal karyotype at presentation and further karyotypic aberrations during his disease course, concomitantly with t he 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.