AACR: Gleevec Sensitizes CLL Cells to Chlorambucil

[Guest guest]

[We have posted on this before. With the high cost of Gleevec,

though, it might be cost prohibitive.]

AACR Abstract Number: 3046

Imatinib sensitizes CLL lymphocytes to chlorambucil

Raquel S. Aloyz, Grzywacz, Zhi-Yuan Xu, Loignon, Moulay

A. Alaoui-Jamali, Lawrence C. Panasci. Lady Institute,

Montreal, PQ, Canada.

The effect of imatinib on chlorambucil (CLB) cytotoxicity in chronic

lymphocytic leukemia (CLL) lymphocytes was examined in vitro.

Imatinib sensitizes the WSU and I83 human CLL cell lines, 10 and 2

fold respectively to CLB. Furthermore, in primary cultures of

malignant B-lymphocytes obtained from 12 patients with CLL (7

patients were untreated and 5 treated with CLB), imatinib

synergistically sensitized these lymphocytes from 2 to 20 fold to

CLB. This synergistic effect was observed at concentrations of

imatinib ( & #8804;10 & #956;M), which are achievable in patients with minimal=

toxicity. Moreover, the combination of both drugs results in

increased apoptosis in CLL cell lines.

These results suggest that imatinib should be useful in improving the

therapeutic index of CLB in CLL. The mechanism of action appears to

involve imatinib inhibition of c-abl kinase activity with an

associated decrease in CLB–induced Rad51 phosphorylation and

chlorambucil-induced Rad51 nuclear foci, suggesting that imatinib

decreases Rad51-related DNA repair of CLB-induced DNA lesions.

Altogether, our results suggest that imatinib is a promising adjuvant

therapy to CLB treatment of CLL.

Presenter: Raquel S. Aloyz

Affiliation: Lady Institute, Montreal, PQ, Canada; E-mail:

raloyz@...

Copyright © 2004 American Association for Cancer Research. All rights

reserved. Citation information: Proceedings of the AACR, Volume 45,

March 2004.