Veridex, Lcc

Mitch Raponi

Yixin Wang

Hongtao Fan

Lesley Estelle Dossey

We analyzed bone marrow from 67 patients from a phase 2 study of farnesyltransferase inhibition with tipifarnib (R115777, ZARNESTRA&#xae;), in older adults with previously untreated, poor-risk acute myeloid leukemia (AML) for N-Ras mutations, global gene expression, and/or quantitative PCR (qPCR) of specific genes. Microarray profiling identified a two-gene expression ratio (RASGRP1:APTX) which provided the greatest accuracy for predicting response to tipifarnib. We demonstrated that this classifier could predict response to tipifarnib in an independent set of 54 samples from relapsed or refractory AML, with a NPV and PPV of 92% and 28%, respectively (odds ratio of 4.4). Therefore, in both newly diagnosed and relapsed or refractory AML, this classifier improves the overall response rate by approximately 50% while maintaining a high NPV, and significantly improves patient overall survival. The two-gene classifier was also validated by qPCR in thirty AML samples from the same clinical study demonstrating a negative predictive value (NPV) and positive predictive value (PPV) of 81% and 50%, respectively (odds ratio of 4.3). These data indicate that a simple two-gene expression assay may have utility in diagnosing a population of AML patients who are more likely to respond to tipifarnib.

Methods of determining acute myeloid leukemia response to treatment with farnesyltransferase

Disclosed in this specification is a method for predicting the prognosis of squamous cell lung cancer by observing regulatory changes in select miRNA sequences. These sequences may include hsa-mir-146b, hsa-mir-191, hsa-mir-206, hsa-mir-299-3p, hsa-mir-155, hsa-mir-15a, hsa-mir-122a, hsa-mir-513, hsa-mir-184, hsa-mir-511, hsa-mir-100, hsa-mir-10a, hsa-mir-453, hsa-mir-379, hsa-mir-202, hsa-mir-21, hsa-mir-126, hsa-mir-494, hsa-mir-432, hsa-mir-370, and combinations of these sequences.

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San Diego, CA, United States of America

Mitch Raponi