Drug resistance testing of acute myeloid leukemia in adults using the MTT assay

Adv Exp Med Biol. 1999;457:445-52. doi: 10.1007/978-1-4615-4811-9_48.

Abstract

Objective: We want to evaluate the MTT in vitro assay for newly diagnosed AML in adults, in particular its prognostic significance.

Methods: MTT tests were performed according to Pieters et al., Blood 76: 2327, 1990. Up to 18 cytostatic drugs were tested in a wide range of concentrations over 4 days and compared with controls. If necessary, blasts were enriched > 80% by negative selection with dynabeads (Kaspers et al., Br. J. Cancer 70: 1047, 1994). Percent S-phase was measured at begin of assay and after 4 days.

Results: Technical success rate was 80-85% and the assay took about one day of work. IC50 values as a measure for drug resistance were highly reproducible with an interassay CV (range) of 28% (13-47) between days. Median cell viability of controls after 4 days was 80% (44-97);% S-phase at begin of assay was 3% (0.1-15) and after 4 days 9% (1-39). Leukemic blasts from 57 adult AML patients were prospectively tested in vitro at diagnosis. Large interindividual differences in drug resistance were observed (over 1000 fold on average). There was a trend for greater IC50 with higher cytogenetic risk and nonresponders to induction. Other clinical prognostic factors such as patient age, initial WBC, FAB subtype, prior MDS and % S-phase did not show a relationship with the in vitro data. There was a high correlation between the topoisomerase II related drugs regarding in vitro resistance.

Conclusion: In vitro sensitivity tests like the MTT assay may provide a valuable tool for prediction of individual therapy outcome in combination with cytogenetics. However, longer follow-up is required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / toxicity*
  • Cell Survival / drug effects
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor / methods*
  • Enzyme Inhibitors / toxicity
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology*
  • Middle Aged
  • Prognosis
  • Regression Analysis
  • Topoisomerase II Inhibitors
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Topoisomerase II Inhibitors