Clinical and proteomic characterization of acute myeloid leukemia with mutated RAS

Abstract

Background: Activating mutations in RAS are frequently present in patients with acute myeloid leukemia (AML), but their overall prognostic impact is not clear. Methods: A retrospective analysis was performed to establish the clinical characteristics of patients with RAS-mutated (RASmut) AML, to analyze their outcome by therapy, and to describe the proteomic profile of RASmut compared with wild-type RAS (RASWT) AML. Results: Of 609 patients with newly diagnosed AML, 11% had RASmut. Compared with RASWT, patients with RASmut AML were younger (median age, 54 years vs 63 years; P =.001), had a higher white blood cell count (16K mm-3 vs 4K mm-3; P < 0.001) and bone marrow blast percentage (56% vs 42%; P =.01) at diagnosis, and were less likely to have an antecedent hematologic disorder (36% vs 50%; P =.03). The inv(16) karyotype was overrepresented in patients with RASmut and the -5 and/or -7 karyotype was underrepresented. RAS mutations were found to have no prognostic impact on overall survival or disease-free survival overall or within cytogenetic subgroups. There was a suggestion that patients with RAS mut benefited from cytarabine (AraC)-based therapy. Proteomic analysis revealed simultaneous upregulation of the RAS-Raf-MAP kinase and phosphoinositide 3-kinase (PI3K) signaling pathways in patients with RAS mut. Conclusions: RAS mutations in AML may delineate a subset of patients who benefit from AraC-based therapy and who may be amenable to treatment with inhibitors of RAS and PI3K signaling pathways. © 2012 American Cancer Society.