Median TSI50,short Values (μmol/L) for MTX and Novel Antifolates and Normalized TSI50,short Ratios in Childhood Leukemia Subtypes
| . | Initial c/preB-ALL . | Relapsed c/preB-ALL (rALL) . | T-ALL . | AML . | |||
|---|---|---|---|---|---|---|---|
| TSI50,short (μmol/L) . | TSI50,short (μmol/L) . | Normalized TSI50,short Ratio . | TSI50,short (μmol/L) . | Normalized TSI50,short Ratio . | TSI50,short (μmol/L) . | Normalized TSI50,short Ratio . | |
| MTX | 0.38 | 1.13-150 | 2.9 | 3.73-151 | 9.8 | 2.23-151 | 5.7 |
| TMQ | 1.5 | 1.3 | 0.853-152 | 1.4 | 0.893-151 | 0.333-151 | 0.223-151 |
| GW1843U89 | 0.0067 | 0.0037 | 0.553-150 | 0.0213-150 | 3.13-153 | 0.0056 | 0.843-151 |
| MTA | 0.21 | 0.33 | 1.63-153 | 1.43-153 | 6.53-153 | 0.41 | 1.93-150 |
| Raltitrexed | 0.0096 | 0.0473-152 | 4.9 | 0.0373-150 | 3.9 | 0.0423-150 | 4.4 |
| . | Initial c/preB-ALL . | Relapsed c/preB-ALL (rALL) . | T-ALL . | AML . | |||
|---|---|---|---|---|---|---|---|
| TSI50,short (μmol/L) . | TSI50,short (μmol/L) . | Normalized TSI50,short Ratio . | TSI50,short (μmol/L) . | Normalized TSI50,short Ratio . | TSI50,short (μmol/L) . | Normalized TSI50,short Ratio . | |
| MTX | 0.38 | 1.13-150 | 2.9 | 3.73-151 | 9.8 | 2.23-151 | 5.7 |
| TMQ | 1.5 | 1.3 | 0.853-152 | 1.4 | 0.893-151 | 0.333-151 | 0.223-151 |
| GW1843U89 | 0.0067 | 0.0037 | 0.553-150 | 0.0213-150 | 3.13-153 | 0.0056 | 0.843-151 |
| MTA | 0.21 | 0.33 | 1.63-153 | 1.43-153 | 6.53-153 | 0.41 | 1.93-150 |
| Raltitrexed | 0.0096 | 0.0473-152 | 4.9 | 0.0373-150 | 3.9 | 0.0423-150 | 4.4 |
TSI50,short values were measured by the in situ TS inhibition assay after a 3-hour drug exposure followed by an 18-hour drug-free period. 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,short was calculated as (TSI50,short for individual sample)/(median TSI50,short for group of c/preB-ALL). Wilcoxon signed ranks test was applied to analyze differences between normalized TSI50,short ratios for a novel antifolate and for MTX. No results are presented for ZD9331 because the majority of the samples required more than the highest concentration tested in this study to inhibit 50% of the TS activity.
P ≤ .001;
P ≤ .01;
P < .05;
P < .1.