Median TSI50,cont. Values (μmol/L) for MTX and Novel Antifolates and Normalized TSI50,cont. Ratios in Childhood Leukemia Subtypes
. | Initial c/preB-ALL . | Relapsed c/preB-ALL (rALL) . | T-ALL . | AML . | |||
---|---|---|---|---|---|---|---|
TSI50,cont. (μmol/L) . | TSI50,cont. (μmol/L) . | Normalized TSI50,cont. Ratio . | TSI50,cont. (μmol/L) . | Normalized TSI50,cont. Ratio . | TSI50,cont. (μmol/L) . | Normalized TSI50,cont. Ratio . | |
MTX | 0.058 | 0.174-150 | 3.0 | 0.080 | 1.4 | 0.051 | 0.88 |
TMQ | 0.022 | 0.022 | 1.0‡ | 0.012 | 0.564-151 | 0.00464-151 | 0.214-151 |
GW1843U89 | 0.0017 | 0.0023 | 1.44-150 | 0.0036 | 2.14-153 | 0.0021 | 1.2 |
MTA | 0.076 | 0.11 | 1.5 | 0.414-151 | 5.44-151 | 0.11 | 1.5‡ |
Raltitrexed | 0.0047 | 0.011‡ | 2.3 | 0.0274-151 | 5.8‡ | 0.0134-150 | 2.8‡ |
ZD9331 | 0.017 | 0.045 | 2.6 | 0.060 | 3.54-151 | 0.017 | 1.0 |
. | Initial c/preB-ALL . | Relapsed c/preB-ALL (rALL) . | T-ALL . | AML . | |||
---|---|---|---|---|---|---|---|
TSI50,cont. (μmol/L) . | TSI50,cont. (μmol/L) . | Normalized TSI50,cont. Ratio . | TSI50,cont. (μmol/L) . | Normalized TSI50,cont. Ratio . | TSI50,cont. (μmol/L) . | Normalized TSI50,cont. Ratio . | |
MTX | 0.058 | 0.174-150 | 3.0 | 0.080 | 1.4 | 0.051 | 0.88 |
TMQ | 0.022 | 0.022 | 1.0‡ | 0.012 | 0.564-151 | 0.00464-151 | 0.214-151 |
GW1843U89 | 0.0017 | 0.0023 | 1.44-150 | 0.0036 | 2.14-153 | 0.0021 | 1.2 |
MTA | 0.076 | 0.11 | 1.5 | 0.414-151 | 5.44-151 | 0.11 | 1.5‡ |
Raltitrexed | 0.0047 | 0.011‡ | 2.3 | 0.0274-151 | 5.8‡ | 0.0134-150 | 2.8‡ |
ZD9331 | 0.017 | 0.045 | 2.6 | 0.060 | 3.54-151 | 0.017 | 1.0 |
TSI50,cont. values were measured by the in situ TS inhibition assay after 21 hours of continuous drug exposure. Mann-Whitney U test was applied to analyze differences between untreated c/preB-ALL and relapsed c/preB-ALL (rALL), T-ALL, or AML. Normalized TSI50,cont. was calculated as (TSI50,cont. for individual sample)/(median TSI50,cont. for group of c/preB-ALL). Wilcoxon signed ranks test was applied to analyze differences between normalized TSI50,cont. ratios for a novel antifolate and for MTX.
P ≤ .01;
P ≤ .001;
P ≤ .05;
P < .1.