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 |
|---|---|
| Pages (from-to) | 245-51 |
| Number of pages | 7 |
| Journal | Blood |
| Volume | 99 |
| Issue number | 1 |
| Publication status | Published - 1 Jan 2002 |
Cite this
}
Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. / 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.
In: Blood, Vol. 99, No. 1, 01.01.2002, p. 245-51.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome
AU - Zwaan, Christian M
AU - Kaspers, Gertjan J L
AU - Pieters, Rob
AU - Hählen, Karel
AU - Janka-Schaub, Gritta E
AU - van Zantwijk, Christina H
AU - Huismans, Dieuwke R
AU - de Vries, Esther
AU - Rots, Marianne G
AU - Peters, Godefridus J
AU - Jansen, Gerrit
AU - Creutzig, Ursula
AU - Veerman, Anjo J P
PY - 2002/1/1
Y1 - 2002/1/1
N2 - 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)
AB - 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)
KW - Amsacrine/pharmacology
KW - Anthracyclines/pharmacology
KW - Antineoplastic Agents/pharmacology
KW - Busulfan/pharmacology
KW - Cell Survival/drug effects
KW - Child
KW - Child, Preschool
KW - Cytarabine/pharmacology
KW - Down Syndrome/complications
KW - Drug Resistance, Neoplasm
KW - Drug Screening Assays, Antitumor
KW - Etoposide/pharmacology
KW - Female
KW - Humans
KW - Infant
KW - Leukemia, Myeloid, Acute/complications
KW - Male
KW - Mitoxantrone/pharmacology
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications
KW - Prednisolone/pharmacology
KW - Prognosis
KW - Thioguanine/pharmacology
KW - Vincristine/pharmacology
M3 - Article
VL - 99
SP - 245
EP - 251
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -