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Supplementary Information for:

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

Sanne Lugthart 1,2,6,8 , Meyling H. Cheok 1,2,8 , Monique L. den Boer 6 , Wenjian Yang 1,2,5 , Amy Holleman 6 , Cheng Cheng 3 , Ching-Hon Pui 1,4,5 , Mary V. Relling 1,2,5 , Gritta E. Janka-Schaub 7 , Rob Pieters 6,9 , William E. Evans 1,2,5,9

1 Hematological Malignancy Program
2 Department of Pharmaceutical Sciences
3 Department of Biostatistics
4 Department of Hematology-Oncology ,St. Jude Children's Research Hospital , Memphis , USA
5 The Pharmacogenetics of Anticancer Agents Research Group in the Pharmacogenetics Research Network, Memphis , Tennessee , USA
6 Department of Pediatric Oncology/Hematology ,Erasmus University Medical Center/Sophia Children's Hospital, ,Rotterdam , The Netherlands
7 COALL study group ,Children's University Hospital , Hamburg , Germany
8 These first authors contributed equally to this work.
9 These last authors contributed equally to this work.

Supplemental Table 8: Overlap in genes discriminating multiple-drug cross-resistance and genes discriminating PRD-, VCR-, ASP- and DNR single-drug resistance.


Summary of the overlapping gene probe sets with corresponding gene symbol (GS), map location (ML) and ratio of the median log-transformed expression signal in cross-resistant versus cross-sensitive ALL for multiple-drug cross-resistance (Ratio). A gene probe set with a ratio of >1 is over-expressed and with a ratio of <1 is under-expressed probe sets in cross-resistant ALL compared to cross-sensitive ALL. The probe sets in overlap between multiple-drug cross-resistance and single-drug resistance to PRD (A), ASP (B) and DNR (C) alone are shown, highlighted in orange and yellow are genes that are in common, no overlap was found with VCR alone. (D) Rows indicate the overlapping genes (n) for single-drug resistance PRD, VCR, ASP, DNR; and columns overlapping genes (n) and percentages for cross-resistance (CR) and VCR-ASP discordant resistance (VA). Overlap occurs in cases the total is not matching the sum of the genes. (1) shows the numbers and the percentages if the significant set of genes identified were compared and (2) shows the results if the analysis is done using the same number of genes for multiple-drug resistance versus single-drug resistance.

A


Probe Set ID

Gene Name

GS

ML

R/S ratio

213061_s_at

N-terminal asparagine amidase

NTAN1

16p13.13

0.60

203274_at

coagulation factor VIII-associated (intronic transcript)

F8A

xq28

0.60

202521_at

CCCTC-binding factor (zinc finger protein)

CTCF

16q21-q22.3

0.66

218438_s_at

endothelial-derived gene 1

EG1

4p16

0.67

219679_s_at

WW domain containing adaptor with coiled-coil

WAC

10p12.1

0.67

208739_x_at

SMT3 suppressor of mif two 3 homolog 2 (yeast)

SUMO2

17q25

0.69

221547_at

PRP18 pre-mRNA processing factor 18 homolog

PRPF18

10p14

0.77

208620_at

poly(rC) binding protein 1

PCBP1

2p13-p12

0.81

217729_s_at

amino-terminal enhancer of split

AES

19p13.3

0.82

205193_at

v-maf musculoaponeurotic fibrosarcoma oncogene

MAFF

22q13.1

1.76

209795_at

CD69 antigen (p60, early T-cell activation antigen)

CD69

12p13-p12

2.14

36711_at

v-maf musculoaponeurotic fibrosarcoma oncogene

MAFF

22q13.1

2.25

218589_at

purinergic receptor P2Y, G-protein coupled, 5

P2RY5

13q14

2.69

B

Probe Set ID

Gene Name

GS

ML

Ratio

203274_at

coagulation factor VIII-associated (intronic transcript)

F8A

xq28

0.60

201140_s_at

RAB5C, member RAS oncogene family

RAB5C

17q21.2

0.63

201156_s_at

RAB5C, member RAS oncogene family

RAB5C

17q21.2

0.76

209604_s_at

GATA binding protein 3

GATA3

10p15

3.38

C

Probe Set ID

Gene Name

GS

ML

Ratio

213061_s_at

N-terminal asparagine amidase

NTAN1

16p13.13

0.60

202777_at

soc-2 suppressor of clear homolog (C. elegans)

SHOC2

10q25

0.61

202521_at

CCCTC-binding factor (zinc finger protein)

CTCF

16q21-q22.3

0.66

218438_s_at

endothelial-derived gene 1

EG1

4p16

0.67

200059_s_at

ras homolog gene family, member A

RHOA

3p21.3

0.82

D



1)

multiple resistance





Overlap

CR (51)

VA (200)

% of CR

% of VA

single

resistance

PRD (42)

13

0

25%

0%

VCR (59)

0

15

0%

8%

ASP (54)

4

36

8%

18%

DNR (22)

5

0

10%

0%



Total (146)

18

51

35%

26%










2)

multiple resistance





Overlap

CR (100)

VA (100)

% of CR

% of VA

single

resistance

PRD (100)

21

0

21%

0%

VCR (100)

1

10

1%

10%

ASP (100)

14

36

14%

36%

DNR (100)

19

1

19%

1%



Total (382)

45

46

45%

47%