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)
Original language | English |
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Pages (from-to) | 245-51 |
Number of pages | 7 |
Journal | Blood |
Volume | 99 |
Issue number | 1 |
Publication status | Published - 1 Jan 2002 |
Keywords
- Amsacrine/pharmacology
- Anthracyclines/pharmacology
- Antineoplastic Agents/pharmacology
- Busulfan/pharmacology
- Cell Survival/drug effects
- Child
- Child, Preschool
- Cytarabine/pharmacology
- Down Syndrome/complications
- Drug Resistance, Neoplasm
- Drug Screening Assays, Antitumor
- Etoposide/pharmacology
- Female
- Humans
- Infant
- Leukemia, Myeloid, Acute/complications
- Male
- Mitoxantrone/pharmacology
- Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications
- Prednisolone/pharmacology
- Prognosis
- Thioguanine/pharmacology
- Vincristine/pharmacology