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Table 5 MTX sensitivity and accumulation of MTX polyglutamates in relation to cytogenetic abnormalities

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

   TSIA cont. TSIA short MTX-Glu1–6 MTX-Glu4–6
Normal cytogenetics N 16 23 18 17
Median (range) 0.048 (0.01–0.71) 0.28 (0.16–2.84) 2102 (436–4240) 1514 (209–3190)
MLL-rearranged N 8 6 4 3
Median (range) 0.06 (0.03–0.16) 0.21 (0.16–1.33) 591 (360–1016) 350 (280–443)
P value 0.610 0.896 0.005* 0.012*
BCR-ABL N 4 2 4 2
Median (range) 0.04 (0.03–0.28) 2088 (360–3721) 1630 (1212–2047)
P value 0.750 0.240 0.712 0.749
TEL-AML1 N 10 9 8 7
Median (range) 0.16 (0.06–0.37) 0.82 (0.54–11.21) 945 (290–2476) 550 (380–1152)
P value 0.023* 0.06 0.013* 0.007*
E2A-PBX1 N 3 3 1 0
Median (range) 0.14 (0.05–0.29) 0.77 (0.57–1.12)
P value 0.254 0.157
  1. First, the Kruskal–Wallis analysis of variance was used to compare all the four groups, and variables with the P value above 0.1 were further examined in detail. The Mann–Whitney U test was used to compare MTX-related variables between each subgroup of ALL patients carrying certain cytogenetic abnormality and patients displaying normal karyotype as a reference group; TSIA continuous (TSIA cont.) 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. The asterisk denotes significant (P < 0.05) associations