In vitro drug resistance profiles of adult acute lymphoblastic leukemia: possible explanation for difference in outcome to similar therapeutic regimens.
Age has important prognostic impact in acute lymphoblastic leukemia (ALL). Adults with ALL have a worse prognosis compared to children. This may be due to different, unfavorable biology, poor treatment tolerance, drug resistance, higher expression of drug resistance related proteins. The lymphoblasts from adult ALL show an increased in vitro resistance to cytotoxic drugs, including prednisolone, dexamethasone, cytosine arabinoside, daunorubicin, L-asparaginase and methotrexate. Glucocorticoid resistance may be a fundamental difference between children, adolescents and adults with ALL, which may underlie different biological aspects and also explain the difference in prognosis. It seems that in vitro resistance to prednisolone with respect to the age might be a continuous variable in ALL patients, except infants. The greater the age, the higher the in vitro resistance to prednisolone. This may be due to induction of various defense mechanisms, such as an activation of P-glycoprotein, which develops throughout the life and protect the human against xenobiotics. Among a number of various drug resistance mechanisms, only several weak differences between adults and children with ALL have been reported including higher P-glycoprotein expression, lower methotrexate polyglutamate accumulation and possibly more often p53 gene mutations in adults. Intrinsic resistance, induction of drug resistance proteins expression during chemotherapy and co-existence of various mechanisms are common phenomena in adult ALL. It seems that age itself, more than drug resistance profile, reflects factors which have direct effect on chemotherapy response in adult ALL.
Styczynski
Jan
J
Department of Pediatric Hematology and Oncology, Medical University, Bydgoszcz, Poland. jan_styczynski@kki.net.pl
Wysocki
Mariusz
M
D000328:Adult; D000367:Age Factors; D002648:Child; D003625:Data Collection; D019008:Drug Resistance, Neoplasm; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D016896:Treatment Outcome