Table 5.

Accumulation and metabolism of aminopterin and methotrexate by patients' leukemic blasts

AntifolylpolyglutamatenTotal intracellular antifolylpolyglutamate (pmol/106 cells), median (range)% Found as antifolylpolyglutamate
(extracellular concentration)Median (range)Compared with Pre-B ALL (P)Aminopterin compared with methotrexate (P)
Methotrexate (1 μmol/L)Pre-B ALL520.64 (0.06-3.55)96 (28-100)
T-ALL210.65 (0.09-2.01)89 (6-100)<0.05
AML190.45 (0.16-3.56)69 (44-100)<0.01
Aminopterin (0.1 μmol/L)Pre-B ALL240.33 (0.08-1.90)100 (83-100)<0.01
T-ALL130.38 (0.11-1.17)100 (73-100)NS<0.05
AML120.35 (0.14-0.51)97 (36-100)<0.05<0.01
  • NOTE: Bone marrow leukemic blasts isolated from patients were incubated with 1 μmol/L [3H]methotrexate or 0.1 μmol/L [3H]aminopterin in vitro. After 24 hours, the cells were collected, washed, and lysed. An aliquot was counted scintillation counter to determine total accumulation, expressed as pmol/106 viable cells. Antifolylpolyglutamates were separated from the parent compounds by high-performance liquid chromatography and compared with known, unlabeled standards.

    Abbreviations: B-ALL, B-lineage ALL; T-ALL, T-phenotype ALL; NS, not significant.