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Blood, Vol. 111, Issue 5, 2589-2596, March 1, 2008
A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia
Blood Raponi et al.
111: 2589
Supplementary material for: Raponi et al
Files in this Data Supplement:
- Document 1. Supplemental materials and methods (PDF, 130 KB)
- Table S1. Profile of newly diagnosed AML cohort (PDF, 86.7 KB)
- Table S2. 45 probesets predictive of response to tipifarnib in newly diagnosed AML (PDF, 44 KB)
- Table S3. Patient characteristics, clinical outcome data and classification status of relapsed and refractory AML cohort (PDF, 60.7 KB)
- Table S4. 93 filtered probe sets from Bullinger prognostic signature (PDF, 44.1 KB)
- Table S5. Characteristics of the Bullinger-CCP classified prognostic groups (PDF, 17.1 KB)
- Table S6. Kaplan-Meier analysis of non-FTI treated AML patients stratified with the RASGRP1:APTX gene expression ratio using different cut-offs (PDF, 16 KB)
- Figure S1. Performance of the RASGRP1 gene as a predictor of response to tipifarnib in AML (JPG, 86 KB)
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The accuracy rates of the RASGRP1 classifier in newly diagnosed AML (A) and relapsed or refractory AML (C) are shown. (B) The overall survival of newly diagnosed AML patients stratified with by RASGRP1 was plotted using Kaplan-Meier analysis. The median overall survival of those predicted to be responders or non-responders was 433 and 76 days, respectively. (D) The overall survival of relapsed/refractory AML patients stratified with the two-gene classifier is shown. The median overall survival of those predicted to be responders or non-responders was 154 and 56 days, respectively.
- Figure S2. Performance of RASGRP1:APTX gene classifier using QPCR (JPG, 67.0 KB)
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(A) Nine RNA samples that were analyzed on both the Affymetrix GeneChip and by qPCR were compared by linear regression analysis. (B) The normalized RASGRP1:APTX Ct values for 20 responders and 10 patients with progressive disease. Twenty independent samples and 10 samples that were run on microarray are plotted. (C) The accuracy rates of the RASGRP1 gene classifier in newly diagnosed AML for all 30 patients are shown using a cutoff of 0 was used to stratify patients. (D) The associated overall survival of the stratified patients was plotted using Kaplan-Meier analysis.
- Figure S3. Overall survival of non-FTI treated AML patients stratified with the RASGRP1:APTX gene expression ratio (JPG, 39.7 KB)
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Three cDNA probes for both RASGRP1 and APTX were present in the Bullinger data set (Gene Expression Omnibus: accession number GSE425). We first calculated the mean value for each gene and then calculated the RASGRP1:APTX ratio of these values. Patients whose ratio was above 1 were classified as progressors and those with a ratio below 1 were classified as responders. Kaplan-Meier analysis was then performed.
- Figure S4. RASGRP1:APTX gene expression and cell line sensitivity to tipifarnib (JPG, 44.1 KB)
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Three AML cell lines (HL60, KG1, THP1) and 3 T-cell ALL cell lines (MOLT4, Jurkat, SUPT1) were assayed for sensitivity to tipifarnib. (A) Representative kill curve for the KG-1 cell line. (B) RNA from each cell line (no tipifarnib control) was harvested at the same time cell counts were performed for the kill curve assay. The RASGRP1:APTX expression ratio was calculated and plotted against the IC50 values. Linear regression analysis was then performed. Low Ct values correspond with high gene expression.
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