Elevated Serum Ras Levels in Patients with LGL Leukemia.

Abstract

Background: Ras is a GDP/GTP binding G protein that acts as a molecular switch converting signals from the cell membrane to the nucleus to regulate cell proliferation, differentiation, and protein synthesis. Activation of ras oncogenes has been identified in a variety of cancers, including 30% of patients with acute myelogenous leukemia (AML). Large granular lymphocyte (LGL) leukemia is a clonal T-cell lymphoproliferative disorder associated with chronic neutropenia, anemia, or autoimmune diseases, particularly rheumatoid arthritis. The purpose of this study was to evaluate serum ras levels in patients with LGL leukemia.Methods: A novel ras p21 ELISA (Oncogene Science/Bayer HealthCare) employing two monoclonal antibodies was utilized to quantify ras levels in baseline serum obtained from 32 patients with LGL leukemia. A control group of 48 healthy subjects was also used to establish a cutoff for the upper limit of normal for serum ras levels. A 95% non-parametric cut-off was used to determine significant differences in the frequency of elevated serum ras levels in control vs. LGL leukemia patients.Results: The median serum ras level in the 48 healthy control subjects was 125 pg/mL, with a 5% to 95% range of 50–422 pg/mL. The upper limit of normal for serum ras was defined as 422 pg/mL, as determined using the 95 % non-parametric cut-off. In the LGL leukemia patient group, 19 of 32 patients (59 %) had elevated baseline serum ras levels (median 484 pg/mL) (p=0.0001) when utilizing the healthy control upper limit of normal cut-off value.Conclusions: The results of this study indicate that the majority of LGL leukemia patients have significantly elevated serum ras levels when compared to healthy controls. Serum ras should be evaluated as a potential biomarker in larger leukemia trials, especially for response to treatment with inhibitors of the ras signaling pathway.