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 (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.

SUBMITTER: Kadia TM 

PROVIDER: S-EPMC3416961 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature