Functional characteristics and gene expression profiles of primary acute myeloid leukaemia cells identify patient subgroups that differ in susceptibility to histone deacetylase inhibitors

  • Authors:
    • Camilla Stapnes
    • Anita Ryningen
    • Kimberley Hatfield
    • Anne Margrete Øyan
    • Geir Egil Eide
    • Matthias Corbascio
    • Karl-Henning Kalland
    • Bjørn Tore Gjertsen
    • Øystein Bruserud
  • View Affiliations

  • Published online on: December 1, 2007     https://doi.org/10.3892/ijo.31.6.1529
  • Pages: 1529-1538
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Abstract

Modulation of gene expression through histone deacetylase (HDAC) inhibition is considered a possible therapeutic strategy in acute myeloid leukaemia (AML). In vitro effects and basal gene expression of structurally different HDAC inhibitors were examined. Primary human AML cells were derived from 59 consecutive patients. The HDAC inhibitors valproic acid, PXD101, trichostatin A and sodium butyrate inhibited leukaemic and clonogenic cell proliferation and increased apoptosis in a dose-dependent manner when tested at high concentrations. However, at lower concentrations proliferation increased for a subset of patients. This divergence was also observed in the presence of all-trans retinoic acid, theophylline and decitabine, and in cocultures with bone marrow stromal cells. Levels of IL-1β, IL-6, GM-CSF and TNFα increased. Based on the basal expression of 100 genes the patients with growth enhancement at intermediate HDAC inhibitor concentrations and those without this response were clustered into two mutually exclusive groups. Functional characterization and gene expression analyses identify AML patient subsets that differ in their response to HDAC inhibitors. These observations may explain why HDAC inhibitor therapy affects only a subset of patients.

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December 2007
Volume 31 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Stapnes C, Ryningen A, Hatfield K, Øyan AM, Eide GE, Corbascio M, Kalland K, Gjertsen BT and Bruserud Ø: Functional characteristics and gene expression profiles of primary acute myeloid leukaemia cells identify patient subgroups that differ in susceptibility to histone deacetylase inhibitors. Int J Oncol 31: 1529-1538, 2007
APA
Stapnes, C., Ryningen, A., Hatfield, K., Øyan, A.M., Eide, G.E., Corbascio, M. ... Bruserud, Ø. (2007). Functional characteristics and gene expression profiles of primary acute myeloid leukaemia cells identify patient subgroups that differ in susceptibility to histone deacetylase inhibitors. International Journal of Oncology, 31, 1529-1538. https://doi.org/10.3892/ijo.31.6.1529
MLA
Stapnes, C., Ryningen, A., Hatfield, K., Øyan, A. M., Eide, G. E., Corbascio, M., Kalland, K., Gjertsen, B. T., Bruserud, Ø."Functional characteristics and gene expression profiles of primary acute myeloid leukaemia cells identify patient subgroups that differ in susceptibility to histone deacetylase inhibitors". International Journal of Oncology 31.6 (2007): 1529-1538.
Chicago
Stapnes, C., Ryningen, A., Hatfield, K., Øyan, A. M., Eide, G. E., Corbascio, M., Kalland, K., Gjertsen, B. T., Bruserud, Ø."Functional characteristics and gene expression profiles of primary acute myeloid leukaemia cells identify patient subgroups that differ in susceptibility to histone deacetylase inhibitors". International Journal of Oncology 31, no. 6 (2007): 1529-1538. https://doi.org/10.3892/ijo.31.6.1529