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Supplementary Information

Gene-expression patterns in drug resistant acute lymphoblastic leukemia cells and response to treatment.

Supplemental Table 7 : Genes previously linked to drug resistance or prognosis in ALL.

Gene expression ratios of resistant (R) and sensitive (S) samples are presented. These genes were not significant at the level required for inclusion in our model (Supplemental Table 4), but those indicated in red were significant at the *P<0.05 or **P<0.001 level.

Category Ratio R/S     Ref.   Category Ratio R/S     Ref.
  PRED VCR ASP DNR       PRED VCR ASP DNR  
Drug efflux pumps:   Apoptosis:
MRP1

1.3

1.01

1.03

1.02

4

  BAD

0.75

0.97

1.09

0.93

5,6

MDR1

1.11

0.99

1.60

0.90

4

  BAK

0.99

1.10

1.06

1.10

5,6

LRP

1.08

0.87

1.06

1.35

4

  BAX

0.96

0.95

1.12

0.85

5,6

BCRP

1.15

0.94

1.01

1.17

7

  BCL2

1.34

1.01

1.13

1.16

5,6

              BCL2:BAX

0.72

0.94

0.99

0.74

5

Drug metabolism:   BCL2L1

0.86

1.28

1.04

0.89

5,6

GSTA1

1.25

0.83

1.14

0.95

8

  BAG1

1.20

0.82

1.26*

1.13

6

GSTM1

1.12

1.04

1.06

1.14

8

  CASP3

1.42

1.30*

0.92

0.98

9

GSTP1

0.96

0.79*

0.94

0.94

8,10

  CD95

0.98

0.96

0.9

0.93

9

MT1E

1.21

0.94

1.24*

1.27*

11

  XIAP

0.74

0.88

0.99

0.94

12

MT1F

1.50

0.81

1.68*

1.60*

11

             
NM23A

0.82

0.78

1.07

1.25

13

  Transcription factors:
              NKFB1

1.22

0.94

0.95

1.13

14

Intracellular drug targets:   RELA

0.93

0.91

1.19

1.00

14

GR

0.97

1.18*

0.97

0.97

15

  FOS

1.23

1.01

1.14

1.50

10

MAP4

0.93

0.82

0.96

0.82

16

  JUN

1.45

0.95

1.35

1.46

10

TUBB1

1.01

1.04

1.20

1.03

16

  WT1

1.29

0.93

2.27*

1.77

17

TUBB4

0.96

0.85

0.91

0.90

16

             
TOP2A

0.84

1.01

1.08

0.94

18

  Miscellaneous:
TOP2B

0.71*

0.95

1.18

0.74

18

  PARP-1

0.97

1.01

1.24

1.21*

19

              HSP27

2.11

1.28

0.79

1.69

20

Cell cycle:   HSP70

2.16

1.39

0.74

1.18

20

MDM2

0.97

1.23

0.96

1.07

14

  HSP90

1.15

0.99

1.04

1.06

21

P15INK4B

1.11

0.78

1.09

1.32

22

  ATM

0.98

1.00

1.24

1.23

23

P16INK4A

0.88

1.07

0.98

0.88

22

  ASNS

0.56

1.48

2.89**

2.08

24

P21

0.90

0.98

0.89*

0.93

25

  GCS

124

1.12

1.81**

1.48

26

TP53

0.78

0.82

1.06

1.13

27

  VEGF

1.27

1.16

0.92

1.17

28

RB1

1.02

0.98

1.03

0.92

29

             
CCND1

1.36

1.49

0.8

0.98

30

             
                           

Red indicates *P<0.05, **P<0.001 for Wilcoxon rank sum test and t-test.

For example, we found that the gene encoding asparagine synthetase (ASNS) was significantly over-expressed in ALL that was resistant to asparaginase, consistent with previously reported differences in the NCI panel of 60 human cancer cell lines.31,32 However, ASNS (P<0.001, Wilcoxon rank sum test; P<0.001, t-test) was not among the 54 most discriminating genes for asparaginase sensitivity, as defined by P<0.0001 (Supplemental Table 4).

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