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Original Article
Clinical and proteomic characterization of acute myeloid leukemia with mutated RAS
Article first published online: 8 MAY 2012
DOI: 10.1002/cncr.27596
Copyright © 2012 American Cancer Society
Additional Information
How to Cite
Kadia, T. M., Kantarjian, H., Kornblau, S., Borthakur, G., Faderl, S., Freireich, E. J., Luthra, R., Garcia-Manero, G., Pierce, S., Cortes, J. and Ravandi, F. (2012), Clinical and proteomic characterization of acute myeloid leukemia with mutated RAS. Cancer, 118: 5550–5559. doi: 10.1002/cncr.27596
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Publication History
- Issue published online: 30 OCT 2012
- Article first published online: 8 MAY 2012
- Manuscript Accepted: 21 FEB 2012
- Manuscript Revised: 16 FEB 2012
- Manuscript Received: 11 OCT 2011
- Abstract
- Article
- References
- Cited By
Keywords:
- acute myeloid leukemia (AML);
- RAS;
- signal transduction;
- cytarabine (AraC)
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 RASmut 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 RASmut.
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. Cancer 2012. © 2012 American Cancer Society.