Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia

Table 1 Results of univariate Cox regression model of MTX resistance-related variables in relation to event-free survival

	Not corrected for protocols			Corrected for protocols
	N	Hazard ratio (95 % CI)	P value	N	Hazard ratio (95 % CI)	P value
TSIA short (cut-off 1.44 μM)
Low	79	1.00		73	1.00
High	23	1. 39 (0.67–2.89)	0.374	22	1.34 (0.60–3.01)	0.477
TSIA continuous (cut-off 0.035 μM)
Low	25	1.00		22	1.00
High	75	1.19 (0.54–2.60)	0.671	70	1.3 (0.53–3.18)	0.567
MTX-Glu_1–6 accumulation (cut-off 1935 pmol/109 cells)
High	29	1.00		29	1.00
Low	79	2.29 (0.96–5.45)	0.062	72	1.73 (0.70–4.27)	0.232
MTX-Glu_4–6 accumulation (cut-off 1000 pmol/109 cells)
High	32	1.00		32	1.00
Low	59	2.61 (1.07–6.36)	0.035*	56	2.23 (0.90–5.57)	0.084
DHFR mRNA (cut-off 3.74)
High	27	1.00		27	1.00
Low	18	1.50 (0.50–4.47)	0.466	18	1.16 (0.37–3.67)	0.796
TS mRNA (cut-off 10)
Low	34	1.00		33	1.00
High	12	0.77 (0.21–2.81)	0.696	12	0.78 (0.21–3.22)	0.781
FPGS mRNA (cut-off 4.13)
High	19	1.00		19	1.00
Low	23	1.17 (0.36–3.83)	0.798	22	0.58 (0.16–2.18)	0.421
FPGH mRNA (cut-off 3.17)
High	16	1.00		15	1.00
Low	18	1.18 (0.32–4.40)	0.805	18	0.80 (0.19–3.33)	0.764
RFC mRNA (cut-off 0.86)
High	19	1.00		19	1.00
Low	25	0.70 (0.23–2.19)	0.544	24	0.36 (0.10–1.32)	0.123
FPGS activity (cut-off 0.35)
High	48	1.00		48	1.00
Low	12	2.32 (0.79–6.80)	0.125	11	2.61 (0.88–7.76)	0.084

TSIA continuous and short-term exposure (TSIA short) are expressed as the concentration of MTX (in μM) necessary to inhibit 50 % of the TS activity (TSI₅₀) compared to the controls incubated without MTX (in triplicate); the concentration of MTX polyglutamates (MTX-Glu_1–6 and MTX-Glu_4–6) is expressed as pmol MTX-Glu_n/10⁹ cells; mRNA expression of folate enzymes is expressed as ratio normalized to β-actin; FPGS activity is expressed as pmol MTX-Glu₂ formed/h/10⁶ cells. The asterisk denotes significant associations

ISSN: 1756-8722