Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia

I. Hubeek; G. J. Peters; A. J.F. Broekhuizen; J. Sargent; B. E.S. Gibson; U. Creutzig; G. J.L. Kaspers

doi:10.1111/j.1365-2141.2005.05760.x

Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia

I. Hubeek
, G. J. Peters
, A. J.F. Broekhuizen
, J. Sargent
, B. E.S. Gibson
, U. Creutzig
, G. J.L. Kaspers

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.

Original language	English
Pages (from-to)	219-222
Number of pages	4
Journal	British journal of haematology
Volume	131
Issue number	2
DOIs	https://doi.org/10.1111/j.1365-2141.2005.05760.x
Publication status	Published - Oct 2005
Externally published	Yes

Keywords

Acute myeloid leukaemia
Childhood leukaemia
Drug resistance

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10.1111/j.1365-2141.2005.05760.x

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Hubeek, I., Peters, G. J., Broekhuizen, A. J. F., Sargent, J., Gibson, B. E. S., Creutzig, U., & Kaspers, G. J. L. (2005). Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia. British journal of haematology, 131(2), 219-222. https://doi.org/10.1111/j.1365-2141.2005.05760.x

@article{9e5ea87ede49455a8ad14587051b4a43,

title = "Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia",

abstract = "To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.",

keywords = "Acute myeloid leukaemia, Childhood leukaemia, Drug resistance",

author = "I. Hubeek and Peters, \{G. J.\} and Broekhuizen, \{A. J.F.\} and J. Sargent and Gibson, \{B. E.S.\} and U. Creutzig and Kaspers, \{G. J.L.\}",

year = "2005",

month = oct,

doi = "10.1111/j.1365-2141.2005.05760.x",

language = "English",

volume = "131",

pages = "219--222",

journal = "British journal of haematology",

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Hubeek, I, Peters, GJ, Broekhuizen, AJF, Sargent, J, Gibson, BES, Creutzig, U & Kaspers, GJL 2005, 'Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia', British journal of haematology, vol. 131, no. 2, pp. 219-222. https://doi.org/10.1111/j.1365-2141.2005.05760.x

Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia. / Hubeek, I.; Peters, G. J.; Broekhuizen, A. J.F. et al.
In: British journal of haematology, Vol. 131, No. 2, 10.2005, p. 219-222.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia

AU - Hubeek, I.

AU - Peters, G. J.

AU - Broekhuizen, A. J.F.

AU - Sargent, J.

AU - Gibson, B. E.S.

AU - Creutzig, U.

AU - Kaspers, G. J.L.

PY - 2005/10

Y1 - 2005/10

N2 - To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.

AB - To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.

KW - Acute myeloid leukaemia

KW - Childhood leukaemia

KW - Drug resistance

UR - https://www.scopus.com/pages/publications/32944466038

U2 - 10.1111/j.1365-2141.2005.05760.x

DO - 10.1111/j.1365-2141.2005.05760.x

M3 - Article

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AN - SCOPUS:32944466038

SN - 0007-1048

VL - 131

SP - 219

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JO - British journal of haematology

JF - British journal of haematology

IS - 2

ER -

Hubeek I, Peters GJ, Broekhuizen AJF, Sargent J, Gibson BES, Creutzig U et al. Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia. British journal of haematology. 2005 Oct;131(2):219-222. doi: 10.1111/j.1365-2141.2005.05760.x

Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia

Abstract

Keywords

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