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.
journal_name
Cancerjournal_title
Cancerauthors
Kadia TM,Kantarjian H,Kornblau S,Borthakur G,Faderl S,Freireich EJ,Luthra R,Garcia-Manero G,Pierce S,Cortes J,Ravandi Fdoi
10.1002/cncr.27596subject
Has Abstractpub_date
2012-11-15 00:00:00pages
5550-9issue
22eissn
0008-543Xissn
1097-0142journal_volume
118pub_type
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