Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia

Internal tandem duplication of the FLT3 gene and point mutations of the N-R AS gene are the most frequent somatic mutations causing aberrant signal-tra nsduction in acute myeloid leukemia (AML). However, their prognostic import ance is unclear. In this study, their prognostic significance was analyzed in 201 newly diagnosed patients with de novo AML except acute promyelocytic leukemia. Three patients had mutations in both genes, 43 had only the FLT3 gene mutation, 25 had only the N-RAS gene mutation, and 130 had neither. T hese mutations seemed to occur independently. Both mutations were related t o high peripheral white blood cell counts, and the FLT3 gene mutation was i nfrequently observed in the French-American-British (FAB)-M2 type. AML case s with wild FLT3/mutant N-RAS had a lower complete remission (CR) rate than those with wild FLT3/wild N-RAS, whereas the presence of mutant FLT3 did n ot affect the CR rate. Univariate analysis showed that unfavorable prognost ic factors for overall survival were age 60 years or older (P = .0002), cyt ogenetic data (P = .002), FAB types other than M2 (P = .002), leukocytosis over 100 +/- 10(9)/L (P = .003), and the FLT3 gene mutation (P = .004). How ever, the N-RAS gene mutation was only a marginal prognostic factor (P = .0 6). For the subjects under 60 years old, multivariate analysis showed that the FLT3 gene mutation was the strongest prognostic factor (P = .008) for o verall survival. The FLT3 gene mutation, whose presence is detectable only by genomic polymerase chain reaction amplification and gel electrophoresis, might serve as an important molecular marker to predict the prognosis of p atients with AML. (C) 1999 by The American Society of Hematology.