Drug Resistance in Childhood Acute Myeloid Leukemia

J.      Styczynski

Abstract

Therapy results in childhood AML differ from those of ALL. The development of drug resistance is the limiting factor in the therapy of AML. Different problems of drug resistance in childhood AML, with emphasis to age and in comparison to adult AML are presented. In vitro and in vivo aspects are discussed, together with mechanisms of resistance to cytostatic drugs, focused on clinical relevance of cellular drug resistance profile and its prognostic value. Possibilities of modulation and circumvention of drug resistance are reviewed, with stress on new drugs being tested. Taking into account both children and adults, it seems that age is adversely related to therapy outcome in AML, and the percentage of patients with favorable cytogenetics decreases with age; however, age is positively correlated with multi-drug resistance and the proportion of patients with unfavorable cytogenetics. AML is considered a stem cell disease. BCRP, PGP and MRPs are preferentially expressed in leukemic stem cells, making this disease drug resistant. Cellular drug resistance in AML cells seems to be similar throughout all other age groups, however the higher the age, the worse the outcome. In childhood AML, no drug is more effective in comparison to ALL, and cellular drug resistance is partially related to chromosomal abnormalities. Pediatric AML is equally resistant as adult AML. Pediatric and adult AML, respectively, are possibly equally drug resistant on initial diagnosis and at relapse. In contrast to ALL, the prognostic value of in vitro drug resistance in childhood AML has not been well documented yet.

Keywords: Acute myeloid leukemia, acute lymphoblastic leukemia, drug resistance, children, adults, prognosis, cytogenetics

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