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

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

  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-Glu1–6 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-Glu4–6 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
  1. 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-Glu1–6 and MTX-Glu4–6) is expressed as pmol MTX-Glun/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