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Supplementary Information

Identification of genes associated with chemotherapy cross-resistance and treatment response in childhood acute lymphoblastic leukemia.

Supplemental Table 6: Transcription factor binding sites over-represented in the sub-cluster of genes over-expressed in VCR-ASP discordant resistant ALL.

The promoter region and the 5'UTR for specific sets of genes was used for MatchT to search the most recent TRANSFAC® Professional 8.1 database (vertebrates) (http://www.biobase.de/) for common regulatory elements. We determined statistical over-representation of the common motifs compared to "all" (~20,000) human promoter sequences (UCSC hg17; CLOVER) (Matys et al., 2003) and additionally we used the promoter sequences of the "other" gene set as background.
We found a total of 152 common transcription factor binding sites in the promoter regions of these 59 genes (3kb 5' of the transcription start site). Furthermore, we found significant over-representation of the same set of common transcription factor binding sites when sequences were compared against either "all" human promoter sequences or against the "other" 200 protein synthesis related genes. All these transcription factors are expressed in ALL cells except HEN1, but only ELF-1 was expressed at a significantly different level in ALL cells that were VCR-sensitive plus ASP-resistant versus VCR-resistance plus ASP-sensitive (P=0.014, t-test, R/S ratio =1.28).

Motif ID Motif TF Raw score P-value from 'all' * P-value from 'other' +
M00069 V$YY1_02 YY1 6.39 0 0.01
M00341 V$GABP_B GABP 1.41 0.001 0.044
M00971 V$ETS_Q6 Ets 2.6 0.002 0.024
M00746 V$ELF1_Q6 ELF-1$ 5.15 0.009 0.012
M00068 V$HEN1_01 HEN1 2.28 0.017 0.003
M00264 V$STAF_02 Staf 3.59 0.023 0.017

* P-value from over-representation compared to "all" ~20,000 human promoter sequences
+ P-value from over-representation compared to promoter sequences of "other" 96 protein synthesis genes
$ P-value <0.05 in the two VCR-ASP discordant resistance phenotypes

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