FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia

The prevalence and significance of genetic abnormalities in older patients with acute myeloid leukemia (AML) are unknown. Polymerase chain reactions a nd single-stranded conformational polymorphism analyses were used to examin e 140 elderly AML patients enrolled in the Southwest Oncology Group study 9 031 for FLT3, RAS, and TP53 mutations, which were found in 34%, 19%, and 9% of patients, respectively. All but one of the FLT3 (46 of 47) mutations we re internal tandem duplications (ITDs) within exons 11 and 12. In the remai ning case, a novel internal tandem triplication was found in exon 11, FLT3 ITDs were associated with higher white blood cell counts, higher peripheral blast percentages, normal cytogenetics, and less disease resistance. All R AS mutations (28 of 28) were missense point mutations in codons 12, 13, or 61. RAS mutations were associated with lower peripheral blast and bone marr ow blast percentages. Only 2 of 47 patients with FLT3 ITDs also had a RAS m utation, indicating a significant negative association between FLT3 and RAS mutations (P = .0013). Most TP53 mutations (11 of 12)were missense point m utations in exons 5 to 8 and were associated with abnormal cytogenetics, es pecially abnormalities in both chromosomes 5 and 7. FLT3 and RAS mutations were not associated with inferior clinical outcomes, but TP53 mutations wer e associated with a worse overall survival (median 1 versus 8 months, P = . 0007). These results indicate that mutations in FLT3, RAS, or TP53 are comm on in older patients with AML and are associated with specific AML phenotyp es as defined by laboratory values, cytogenetics, and clinical outcomes.