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Supplementary Information

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

Supplemental Table 1: Characteristics of patients within each group classified as cross-resistant and VCR-ASP discordant resistant ALL.

The ALL subtypes of the 129 patients for whom gene expression was performed included 40 with the TEL-AML1 gene fusion t(12;21), 33 hyperdiploid (>50 chromosomes), six with the E2A-PBX1 gene fusion t(1;19), five with the BCR-ABL gene fusion t(9;22) and three with the MLL-AF4 gene fusion  t(4;11). The remaining 40 B-lineage ALLs were negative for all five of these genetic subtypes. White blood cell count at diagnosis (WBC), age at diagnosis and sex in patients defined as cross-resistant (n=29) or cross-sensitive (n=38) by the CR-score. Patients with VCR-sensitive plus ASP-resistant ALL (VCR-S+ASP-R, n=42) or VCR-resistant ALL plus ASP-sensitive (VCR-R+ASP-S, n=34), as defined by the VCR-ASP discordant resistance phenotype. TEL-AML1 translocation and hyperdiploidy showed a trend of higher prevalence in younger children, but was not statistically significant in our population (P=0.1074, ANOVA). Sixteen of 34 (47%) ALLs that were VCR-resistant plus ASP-sensitive compared to only three of 42 (7%) that were VCR-sensitive plus ASP-resistant, had the t(12;21) translocation yielding the TEL-AML1 gene fusion (P=0.0001, Fisher's exact test). Fifteen of 34 (44%) ALLs that were VCR-resistant plus ASP-sensitive, compared to only four of 42 (10%) that were VCR-sensitive plus ASP-resistant, were hyperdiploid (P=0.001, Fisher's exact test). All 19 TEL-AML1 positive and 19 hyperdiploid ALLs grouped together in one branch in the hierarchical clustering using the 200 probe sets discriminating VCR-ASP-discordant resistance (Supplemental Figure 6A).

  Cross-sensitive Cross-resistant P-value* VCR-R+ASP-S VCR-S+ASP-R P-value*
Sex            
Female 15 12 1.00 16 19 1.00
Male 23 17   18 23  
Age            
<10 years 34 16 0.002 27 28 0.30
>10 years 4 13   7 14  
WBC            
<50/nL 24 20 0.80 23 27 0.81
>50/nL 14 9   11 15  
ALL subtype            
B-lineage other 9 18 0.006 3 25 <0.0001
BCR-ABL 2 1   0 5  
E2A-PBX1 5 0   0 3  
MLL-AF4 0 1   0 2  
TEL-AML1 11 6   16 3  
Hyperdiploid 11 3   15 4  

* Fisher's exact test

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