Cellular drug resistance in acute myeloid leukemia: literature review and preliminary analysis of an ongoing collaborative study

Cellular drug resistance is one of the main causes of the frequent ultimate failure of chemotherapy in childhood acute myeloid leukemia (AML). We here summarize the results of a literature review on in vitro drug resistance i n childhood AML, focusing on studies using so-called cell culture assays. W e also briefly describe some results of an ongoing collaborative study betw een the Research Laboratory of Pediatric Oncology in Amsterdam (University Hospital Vrije Universiteit) and the German BFM-AML Group. In general, the literature and our preliminary data on in vitro cellular drug resistance in AML are promising in terms of clinical relevance. Cell biological features and clinical response to chemotherapy are related to in vitro drug resista nce. However, a large study including multivariate analysis is required to more firmly establish the clinical value of cellular drug resistance testin g in childhood AML, and the collaborative study will therefore be continued . Possible applications of cell culture assays include risk-group stratific ation, rational improvements of current treatment protocols for subgroups o f patients based on specific drug resistance profiles, individualised tailo red therapy, the study of cross-resistance patterns between drugs, the stud y of possibilities to modulate or circumvent drug resistance, the study of drug interactions, selection of patients for clinical phase II studies and drug screening.