SIGNIFICANCE OF CHROMOSOMAL ALTERATIONS AND MUTATIONS OF THE N-RAS AND TP53 GENES IN RELATION TO LEUKEMOGENESIS OF ACUTE MYELOID-LEUKEMIA

We examined chromosomes and mutations of the N-RAS and TP53 genes in 7 3 patients with acute myeloid leukemia (AML). Twenty-six patients show ed a reciprocal chromosomal translocation or an inversion, and 34 pati ents showed only unbalanced aberrations. Balanced aberrations were pre dominantly detected in the AML patients who did not have myelodysplasi a, preceding myelodysplastic syndrome, and a history of chemotherapy o r radiation therapy. In contrast, unbalanced aberrations were more fre quently seen in the patients with AML with trilineage myelodysplasia, AML transformed from MDS, and therapy-related AML. Twenty-two mutation s of the N-RAS and TP53 genes were detected, and these mutations were frequently associated with unbalanced chromosomal aberrations. Further more, the spectrum of mutations was suggestive of an exposure to alkyl ating chemicals. (C) 1998 Elsevier Science Ltd. All rights reserved.