Correlation of RASGRP1:APTX expression assay with response to tipifarnib plus etoposide in elderly patients with newly diagnosed AML.

6534 Background: A two-gene ratio (RASGRP1:APTX) has previously been shown to be associated with response to the single agent farnesyltransferase inhibitor (FTI), tipifarnib, in patients with both newly diagnosed or relapsed and refractory acute myeloid leukemia (AML) (Raponi et al. Blood 2008, 111:2589). Here we demonstrated the utility of the 2-gene ratio to correlate with response to the combination therapy with tipifarnib and etoposide in an independent patient cohort of elderly patients with newly diagnosed AML from a Phase 2 study (Karp et al. Blood 2009, 113:4841). Methods: Taqman-based quantitative RT-PCR assays were designed and optimized in RUO and GMP formats for two tipifarnib-specific markers RASGRP1 and APTX, and an internal control marker HMBS, and successfully performed on pretreatment bone marrow aspirates of 32 patients evaluable for response. Results: A receiver operator characteristic analysis indicated a high correlation between both RT-PCR formats (Pearson R2 range for 3 markers, 0.9...