Correlation of drug-perturbed marrow cell growth kinetics and intracellular 1-B-D-arabinofuranosylcytosine metabolism with clinical response in adult acute myelogenous leukemia.

摘要: To define the relationship between leukemic cell growth, intracellular metabolism of 1-B-D-arabinofuranosylcytosine (ara-C), and clinical response to timed sequential induction therapy with ara-C in adult acute myelogenous leukemia (AML), growth kinetic biochemical pharmacologic determinants were examined AML bone marrow populations. Leukemic blasts from 45 previously untreated patients obtained prior cultured vitro autologous pretreatment serum (APS) containing drug-induced humoral stimulatory activity (HSA). Cell populations HSA demonstrated both increased proliferation, as measured by [3H]dThd incorporation into DNA blast labeling index, greater [3H] index relative cells maintained APS. HSA-cultured 31 who achieved complete remission ara-C-containing enhanced formation 5'-triphosphate over three hours retention this active form during one subsequent hour drug-free medium In contrast, 14 nonresponsive no such HSA-induced increases metabolism. These studies human identify behavior patterns activation net kinetically perturbed, proliferative state that may discriminate sensitivity resistance ara-C-based therapy. Sensitive behave similarly normal hematopoietic cohorts, direct linkage HSA-perturbed parameters, while refractory demonstrate uncoupling these growth-stimulated state. measurements further serve a template for prediction outcome ara-C, where cytokinetic are intrinsic success designed drug scheduling.