Correlations Between the In Situ TSIA and MTX Accumulation or MTX Polyglutamylation
. | Total MTX Accumulation (pmol/109 cells) . | Percentage MTX-Glu4-6 . | ||||
---|---|---|---|---|---|---|
r . | P . | n . | r . | P . | n . | |
TSI50,cont. MTX (μmol/L) | −.51 | <.001 | 47 | −.03 | .87 | 42 |
TSI50,short MTX (μmol/L) | −.58 | <.001 | 43 | −.29 | .07 | 39 |
TSI50,shortMTX/TSI50,cont. MTX | −.28 | .14 | 30 | −.48 | .01 | 27 |
. | Total MTX Accumulation (pmol/109 cells) . | Percentage MTX-Glu4-6 . | ||||
---|---|---|---|---|---|---|
r . | P . | n . | r . | P . | n . | |
TSI50,cont. MTX (μmol/L) | −.51 | <.001 | 47 | −.03 | .87 | 42 |
TSI50,short MTX (μmol/L) | −.58 | <.001 | 43 | −.29 | .07 | 39 |
TSI50,shortMTX/TSI50,cont. MTX | −.28 | .14 | 30 | −.48 | .01 | 27 |
Spearman’s correlation coefficients (r) of TSI50 values for MTX of patient-derived leukemic blast cells obtained with the TSIA and MTX accumulation over 24 hours in 1 μmol/L [3H]-MTX or polyglutamylation efficiency defined as percentage of total accumulated MTX present as MTX-Glu4-6. For T-ALL, median accumulation of MTX was 630 pmol/109 cells (range, 314 to 1316 pmol/109cells), median percentage MTX-Glu4-6 was 41% (range, 0% to 85%). For c/preB-ALL, median accumulation of MTX was 1364 pmol/109 cells (range, 521 to 3068 pmol/109cells), median percentage MTX-Glu4-6 was 72% (range, 34% to 82%). TSI50 values were determined either after 21 hours continuous MTX exposure (TSI50,cont.) or after 3 hours of MTX incubation followed by an 18-hour drug-free period (TSI50,short).