The Serenity Prayer for acute GVHD.

expression to predict the clinical response to tipifarnib and etoposide. RASGRP1 is a guanine nucleotide exchange factor (GEF) that specifically activates RAS, and Aprataxin is a member of the histine triad family of nucleotide hydrolsases involved in the repair of DNA strand breaks. 3 The two-gene expression ratio (RASGRP1/APTX) was identified by analyzing gene expression profiles in bone marrow samples from older patients with previously untreated AML in a phase 2 study of tipifarnib. The results were validated in an independent set of samples from relapsed or refractory AML with negative predictive and positive predictive values of 92% and 28%, respectively (odds ratio of 4.4). The two-gene signature also predicted for improved overall survival (154 vs 56 days; P Ͻ .001). 3 Here, Karp and colleagues confirmed the two-gene signature correlated with clinical response in a cohort of the elderly AML patients treated with tipifarnib and etoposide. Patients with a RASGRP1:APTX ratio of Ն 5.2 had a CR rate of 78% compared with those with a ratio of Ͻ 5.2 who had a CR rate of only 13%. The two-gene ratio did not correlate with outcome in other patients treated with conventional chemotherapy. 1 The report by Karp et al contains important information in the search for the most effective way to use tipifarnib in the treatment of elderly AML. Technologies such as mi-croarray gene expression assays may be paving the way to a better understanding of which genetic lesions are involved in the biology of AML and drug resistance, and thus possibly allowing for a more effective and perhaps per-sonalized selection of appropriate therapies. Further work needs to be done to clarify whether the two-gene signature expression ratio has utility for other classes of FTIs and whether a qPCR assay can be applied in clinical practice. Conflict-of-interest disclosure: The author declares no competing financial interests. ■ REFERENCES 1. Karp JE, Vener TI, Raponi M, et al. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia. Suppression of farnesyltransferase activity in acute myeloid leukemia and myelodysplastic syndrome: current understanding and recommended use of tipifarnib. A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia. the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in medullary and differentiated thyroid malignancies. A phase 2 study of …