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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 10: Proportional-hazards regression analysis.

Single factor proportional-hazards regression analysis of the risk of relapse in relation to known prognostic factors (i.e., white blood cell count (WBC), age at diagnosis) and cross-resistance and VCR-ASP discordant resistance gene expression scores are shown in Table (A) for COALL/DCOG patients and in Table (B) for St. Jude patients. Multiple proportional-hazards regression analysis of known prognostic factors (i.e., WBC, age) and gene expression scores are shown in Table (C) for COALL/DCOG patients and in Table (D) for St. Jude patients.

Variable	n	HR	95% C.I.	P-value	n	HR	95% C.I.	P-value
Age
<10 years	96	1.0*			57	1.0*
>10 years	33	2.36	1.10-5.05	0.03	26	3.46	1.12-10.64	0.03
WBC
<49/nL	91	1.0*			50	1.0*
50-100/nL	20	0.88	0.26-3.03	0.84	16	3.05	0.76-12.2	0.12
>100/nL	18	3.82	1.69-8.67	0.0013	17	3.7	0.92-14.9	0.065
ALL subtype
B-other	42	1.0*			27	1.0*
BCR-ABL	5	2.49	0.72-8.64	0.15	8	11.65	2.50-54.0	0.0017
E2A-PBX1	6	0.93	0.21-4.07	0.92	12	0.76	0.08-6.83	0.81
Hyperdiploid	33	0.22	0.06-0.77	0.017	15	0.58	0.06-5.32	0.63
MLL-AF4	3	28.49	6.30-128.9	<0.0001	5	5.13	0.77-34.1	0.09
TEL-AML1	40	0.11	0.03-0.50	0.0038	16	0.57	0.06-5.33	0.63
GE score (CR)
Low⁺	33	1.0*			(8)	**	**	**
Intermediate	63	2.31	0.65-8.18	0.2	73	1.0*
High^‡	33	5.99	1.7-21.09	0.0053	10	7.76	2.44-24.7	0.0005
GE score (VA)
Low⁺	33	1.0*			16	1.0*
Intermediate	64	3.59	0.81-15.9	0.09	52	1.16	0.24-5.57	0.86
High^‡	32	9.04	2.04-40.1	0.0038	15	1.67	0.28-10.03	0.57

Variable	n	HR	95% C.I.	P-value	n	HR	95% C.I.	P-value
Age
<10 years	96	1.0*			57	1.0*
>10 years	33	2.23	0.93-5.38	0.074	26	2.99	0.71-12.6	0.14
WBC
<49/nL	91	1.0*			50	1.0*
50-100/nL	20	0.98	0.27-3.5	0.98	16	4.70	1.0-22.1	0.05
>100/nL	18	5.06	2.05-12.5	0.0005	17	4.87	1.08-21.93	0.039
GE score CR
Low⁺	33	1.0*			(8)	**	**	**
Intermediate	63	2.09	0.58-7.6	0.26	73	1.0*
High^‡	33	3.82	0.95-15.4	0.06	10	5.06	1.28-20.03	0.021
GE score VA
Low⁺	33	1.0*			16	1.0*
Intermediate	64	2.76	0.61-12.47	0.19	52	0.36	0.06-2.24	0.27
High^‡	32	4.31	0.89-20.8	0.069	15	0.61	0.09-4.12	0.61

*reference group, **no relapses in this group, hazard ratio cannot be computed
^‡top quartile; CR, cross-resistant ALL; VA, VCR-sensitive +ASP-resistant ALL
⁺bottom quartile; CR, cross-sensitive ALL; VA, VCR-resistant+ASP-sensitive ALL