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Blood, 1 January 2002, Vol. 99, No. 1, pp. 245-251
NEOPLASIA
Different drug sensitivity profiles of acute myeloid and
lymphoblastic leukemia and normal peripheral blood mononuclear cells in
children with and without Down syndrome
Christian M. Zwaan,
Gertjan
J. L. Kaspers,
Rob Pieters,
Karel Hählen,
Gritta E. Janka-Schaub,
Christina H. van
Zantwijk,
Dieuwke R. Huismans,
Esther de
Vries,
Marianne G. Rots,
Godefridus J. Peters,
Gerrit Jansen,
Ursula Creutzig, and
Anjo J. P. Veerman
From the Departments of Pediatric Hematology/Oncology,
Medical Oncology, and Rheumatology, Vrije Universiteit Medical Center,
Amsterdam, The Netherlands; the Department of Oncology/Hematology,
Sophia Children's Hospital/University Hospital Rotterdam, The
Netherlands; the Dutch Childhood Leukemia Study Group, Den Haag, The
Netherlands; the CoALL Study Group, University Hospital Eppendorf,
Hamburg, Germany; the Department of Pediatrics, Bosch Medicentrum,
`s-Hertogenbosch, The Netherlands; and the AML-BFM Study Group,
University Children's Hospital Münster, Germany.
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.
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