title: Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome.
abstract: Children with Down syndrome (DS) have an increased risk for leukemia. The prognosis for DS acute myeloid leukemia (AML) is better than for non-DS AML, but the clinical outcome of DS acute lymphoblastic leukemia (ALL) is equal to that of non-DS ALL. Differences in prognosis may reflect differences in cellular drug resistance. In vitro drug resistance profiles were successfully investigated on leukemic cells from 13 patients with DS AML and 9 patients with DS ALL and were compared with reference data from 151 non-DS AML and 430 non-DS B-cell precursor (BCP) ALL. DS AML cells were significantly more sensitive to cytarabine (median, 12-fold), the anthracyclines (2-7-fold), mitoxantrone (9-fold), amsacrine (16-fold), etoposide (20-fold), 6-thioguanine (3-fold), busulfan (5-fold), vincristine (23-fold), and prednisolone (more than 1.1-fold), than non-DS AML cells. Compared with DS ALL, DS AML cells were significantly more sensitive to cytarabine only (21-fold). After short-term exposure to methotrexate, DS AML cells were 21-fold more resistant than non-DS AML cells, but no difference was observed after continuous exposure. DS ALL cells and non-DS BCP-ALL cells were equally sensitive to all drugs, including methotrexate. Normal peripheral blood mononuclear cells from DS and non-DS children without leukemia showed highly resistant drug profiles. It was concluded that the better prognosis of DS AML might, at least partially, be explained by a specific, relatively sensitive drug-resistance profile, reflecting the unique biology of this disease. (Blood. 2002;99:245-251)
authors.affiliation: Department of Pediatric Hematology/Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. cm.zwann@vumc.nl
authors.forename: Christian M
authors.initials: CM
authors.lastname: Zwaan
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Karel
authors.initials: K
authors.lastname: Hählen
authors.forename: Gritta E
authors.initials: GE
authors.lastname: Janka-Schaub
authors.forename: Christina H
authors.initials: CH
authors.lastname: van Zantwijk
authors.forename: Dieuwke R
authors.initials: DR
authors.lastname: Huismans
authors.forename: Esther
authors.initials: E
authors.lastname: de Vries
authors.forename: Marianne G
authors.initials: MG
authors.lastname: Rots
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Gerrit
authors.initials: G
authors.lastname: Jansen
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Anjo J P
authors.initials: AJ
authors.lastname: Veerman
mesh_terms: D000677:Amsacrine / Q000494:pharmacology; D018943:Anthracyclines / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002066:Busulfan / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000494:pharmacology; D004314:Down Syndrome / Q000150:complications*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008942:Mitoxantrone / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D011239:Prednisolone / Q000494:pharmacology; D011379:Prognosis; D013866:Thioguanine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D000677:Amsacrine; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D011239:Prednisolone; D008942:Mitoxantrone; D013866:Thioguanine; D002066:Busulfan