Affordable Access

The rho-kinase inhibitors Y-27632 and fasudil act synergistically with imatinib to inhibit the expansion of ex vivo CD34(+) CML progenitor cells.

Authors
  • Burthem, J
  • Rees-Unwin, K
  • Mottram, R
  • Adams, J
  • Lucas, G S
  • Spooncer, E
  • Whetton, A D
Type
Published Article
Journal
Leukemia
Publication Date
Aug 01, 2007
Volume
21
Issue
8
Pages
1708–1714
Identifiers
PMID: 17554385
Source
Medline
License
Unknown

Abstract

Evidence from cell line-based studies indicates that rho-kinase may play a role in the leukaemic transformation of human cells mediated by the BCR/ABL tyrosine kinase, manifest clinically as chronic myeloid leukaemia (CML). We therefore employed two separate inhibitors, Y-27632 and fasudil, to inhibit the activity of rho-kinase against ex vivo CD34(+) cells collected from patients with CML. We compared the effects of rho-kinase inhibition in those cells with the effects of direct inhibition of BCR/ABL using the specific inhibitor imatinib. We found that inhibition of rho-kinase inhibited the effective proliferation, and reduced survival of CML progenitor cells. When combined with imatinib, rho-kinase inhibition added to the anti-proliferative and pro-apoptotic effects of the BCR/ABL inhibitor. Our studies may indicate therapeutic benefit in some cases for the combination of rho-kinase inhibitors with imatinib.

Report this publication

Statistics

Seen <100 times