Methods of determining acute myeloid leukemia response to treatment with farnesyltransferase
First Claim
1. A method of determining the response to tipifarnib in a person with acute myeloid leukemia (AML) comprising:
- a) measuring the expression of RASGRP1 in a biological sample from the person, b) measuring the expression of APTX in a biological sample from the person, c) determining the ratio of the expression of RASGRP1 to that of APTX, and d) identifying the person as one who will respond to tipifarnib if the ratio is less than one.
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Abstract
We analyzed bone marrow from 67 patients from a phase 2 study of farnesyltransferase inhibition with tipifarnib (R115777, ZARNESTRA®), 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.
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2 Claims
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1. A method of determining the response to tipifarnib in a person with acute myeloid leukemia (AML) comprising:
- a) measuring the expression of RASGRP1 in a biological sample from the person, b) measuring the expression of APTX in a biological sample from the person, c) determining the ratio of the expression of RASGRP1 to that of APTX, and d) identifying the person as one who will respond to tipifarnib if the ratio is less than one.
- View Dependent Claims (2)
Specification