|
|
An analysis of the clinical and biological significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma
Blood Xiong et al.
10.1182/blood-2007-10-119123
Supplemental materials for: Xiong et al
Files in this Data Supplement:
- Table S1. SAM analyses results of 85 TP53 induced genes in high- and low- TP53 patients (PDF, 43 KB)
- Figure S1. Low TP53 expression (JPG, 116 KB)
-
(A) Low TP53 expression negatively influences post-relapse survival. The 90 patients on TT2 with relapsed MM were divided into two groups based on the TP53 Affymetrix signal being less than or greater than 733. Kaplan-Meier estimates show 5-year actuarial probabilities of 14% alive in cases with TP53 < 733 versus 35% alive in cases with TP53 >733 (P < 0.05). (B) Low TP53 expression negatively influences survival in an independent cohort. The 214 patients newly diagnosed with MM enrolled on TT3 were divided into two groups based on TP53 expression level being less than or greater than 733. Kaplan-Meier estimates show 2-year actuarial probabilities of (i) 63% being event free and (ii) 66% alive among cases with TP53 <733 versus 81% event-free and 88% alive among those with TP53 >733 (P < 0.05). (C) Low TP53 expression influences survival in molecular risk classes in MM. When TP53 expression was put in the context of a recently described risk stratification model,1 Kaplan-Meier estimates of 5-year actuarial probabilities of (i) 34% being event-free and (ii) 52% being alive among cases with low risk and TP53 Affymetrix signal <733 compared to 55% event-free and 69% alive among cases with low risk and TP53 signal >733 (P < 0.005).
- Figure S2. TP53 target genes (JPG, 197 KB)
-
(A) Heatmap of 122 TP53 target genes in 351 newly diagnosed MM patients on TT2, 214 patients on TT3, and 90 relapsed-MM patients on TT2. (B) The normalized log ratio of the 122 TP53 target genes in the overexpression experiments involving four MM cell lines.
- Figure S3. Networks of TP53-regulated genes in MM cell lines and patients (JPG, 63.6 KB)
-
Ingenuity Pathways Analysis software was used to analyze the identified genes (n = 85). Three networks were identified. The main network was shown in Figure 5. The genes written in bold letters with a shaded node were identified by microarray analysis, and the other genes were those related to the regulated genes on the basis of the network analysis. The intensity of a node color indicates the degree of up-regulation (red). The meanings of node shapes are indicated in the figure. (A) The network represents proteins involved in the biological functions of the cell cycle and cellular movement, assembly, and organization. (B) The network represents proteins involved in the biological functions of cell morphology and DNA replication, recombination, and repair.
- Figure S4. Gene expression profiles of TP53-regulated genes and their clinical relevance (JPG, 105 KB)
-
Two-dimensional unsupervised hierarchical cluster analysis of 85 (rows) TP53-regulated genes in CD138-enriched plasma cells from (A-i) patients with relapsed MM on TT2 (n=90) and (B-i) newly diagnosed MM patients on TT3 (n=214). The right branch consists of MM samples that have a gene expression profile associated with high TP53 expression (horizontal green bar), and the left branch contains MM samples that have a gene expression profile associated with low TP53 expression (horizontal red bar). Kaplan-Meier estimates of post-relapse survival in 90 relapsed-MM patients (A-ii) on TT2 showed superior 5-year actuarial probabilities of post-relapse survival (55% vs. 17%; P < 0.0001) and in (A-i) the right-branch patients with an 85-gene expression profile associated with high TP53 expression. Kaplan-Meier estimates of EFS (B-ii)and OS (B-iii) in newly diagnosed MM patients on TT3 showed superior 3-year actuarial probabilities of EFS (88% vs. 68%; P = 0.0018) and OS (89% vs. 78%; P = 0.0625) in (B-i) the right-branch patients with an 85-gene expression profile associated with high TP53 expression.
| |
