Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome

• Published in: Blood 2002-01, Vol.99 (1), p.245-251
• Main Authors: Zwaan, Christian M., Kaspers, Gertjan J.L., Pieters, Rob, Hählen, Karel, Janka-Schaub, Gritta E., van Zantwijk, Christina H., Huismans, Dieuwke R., de Vries, Esther, Rots, Marianne G., Peters, Godefridus J., Jansen, Gerrit, Creutzig, Ursula, Veerman, Anjo J.P.
• Format: Article
• Language: English
• Subjects: Amsacrine - pharmacology; Anthracyclines - pharmacology; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Busulfan - pharmacology; Cell Survival - drug effects; Child; Child, Preschool; Chromosome aberrations; Cytarabine - pharmacology; Down Syndrome - complications; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Etoposide - pharmacology; Female; Hematologic and hematopoietic diseases; Humans; Infant; Leukemia, Myeloid, Acute - complications; Leukemia, Myeloid, Acute - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical genetics; Medical sciences; Mitoxantrone - pharmacology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Prednisolone - pharmacology; Prognosis; Thioguanine - pharmacology; Vincristine - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.1.245

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.