Alexander Dobrovic, Ph.D. Peter MacCallum Cancer Centre (Australia)

THERAPY/ PROGNOSTIC

Identifying Therapeutic Targets by Profiling DNA repair in CLL

Update:

Personalized medicine involves treating each patient with CLL in an individualized fashion taking into account the specific alterations in the leukemia cells. This project involves identifying those individual differences that occur in CLL, particularly those in DNA repair and cell death that might make the CLL cancer cells sensitive to particular therapies.

For this project, we required purified leukemic cells and developed a new way to do this by removing the normal cells in the blood (Essakali et al, 2008). We then used a new all-exon array methodology that surveys the expression of every known gene in humans. Our plan is to identify differences that occur in gene expression in the abnormal cells which might be targeted by existing or future therapies which can selectively kill the cancer cells while leaving the normal cells intact. We identified a new mechanism that makes CLL resistant to some therapies as well as deficiencies of DNA repair in individual patients which may be useful as potential targets (Essakali et al, in preparation).

Essakali S, Carney D, Westerman D, Gambell P, Seymour JF, Dobrovic A. Negative selection of chronic lymphocytic leukaemia cells using a bifunctional rosette-based antibody cocktail. BMC Biotechnol. 2008 Jan 29;8:6