Elevated Serum Ras Levels in Patients with LGL Leukemia.

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.