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, Anjo J P Veerman

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)245-51
Number of pages7
JournalBlood
Volume99
Issue number1
Publication statusPublished - 1 Jan 2002

Cite this

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. / Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. In: Blood. 2002 ; Vol. 99, No. 1. pp. 245-51.
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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)",
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author = "Zwaan, {Christian M} and Kaspers, {Gertjan J L} and Rob Pieters and Karel H{\"a}hlen and Janka-Schaub, {Gritta E} and {van Zantwijk}, {Christina H} and Huismans, {Dieuwke R} and {de Vries}, Esther and Rots, {Marianne G} and Peters, {Godefridus J} and Gerrit Jansen and Ursula Creutzig and Veerman, {Anjo J P}",
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Zwaan, CM, Kaspers, GJL, Pieters, R, Hählen, K, Janka-Schaub, GE, van Zantwijk, CH, Huismans, DR, de Vries, E, Rots, MG, Peters, GJ, Jansen, G, Creutzig, U & Veerman, AJP 2002, 'Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome' Blood, vol. 99, no. 1, pp. 245-51.

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 journalArticleAcademicpeer-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 -