Clinical and proteomic characterization of acute myeloid leukemia with mutated RAS.

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 (RAS(mut) ) AML, to analyze their outcome by therapy, and to describe the proteomic profile of RAS(mut) compared with wild-type RAS (RAS(WT) ) AML.

RESULTS

Of 609 patients with newly diagnosed AML, 11% had RAS(mut) . Compared with RAS(WT) , patients with RAS(mut) 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 RAS(mut) 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.