Dual inhibition of the homologous recombinational repair and the nonhomologous end-joining repair pathways in chronic lymphocytic leukemia therapy

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BlankDual inhibition of the homologous recombinational repair and the

nonhomologous end-joining repair pathways in chronic lymphocytic leukemia

therapy.

L Amrein, D son, M Shawi, L Petruccelli, W , R Aloyz, and L Panasci

Leuk Res, January 29, 2011; .

Department of Oncology, Segal Cancer Center, Lady Institute, Jewish

General Hospital, McGill University, Montreal, QC, Canada.

Resistance to chlorambucil in chronic lymphocytic leukemia (CLL) has been

associated with increased DNA repair. Specifically, inhibition of either c-abl,

which modulates Rad51 directed homologous recombination or DNA-PK dependent

nonhomologous end joining has been shown to sensitize primary CLL lymphocytes to

chlorambucil. Here we report that inhibition of c-abl can result in a

compensatory increase in DNA-PK and thus inhibition of both c-abl and DNA-PK

optimally sensitizes CLL lymphocytes to chlorambucil. In this paper we report a

drug-induced compensatory change between two DNA repair pathways with potential

therapeutic implications in CLL therapy.

PMID: 21281966