Inhibition of Bcl-xL expression sensitizes T-cell acute lymphoblastic leukemia cells to chemotherapeutic drugs

Broome, H.Elizabeth; Yu, Alice L; Diccianni, Mitch; Camitta, Bruce M; Monia, Brett P; Dean, Nicholas M

« Previous Next »Leukemia Research
Volume 26, Issue 3 , Pages 311-316, March 2002

Inhibition of Bcl-xL expression sensitizes T-cell acute lymphoblastic leukemia cells to chemotherapeutic drugs

H.Elizabeth Broome
- University of California, San Diego Medical Center, 200 West Arbor Drive, Mail Code 8320, San Diego, CA 92103, USA
- Corresponding author. Tel.: +1-619-543-2395; Fax: +1-619-543-3730
Alice L Yu
- University of California, San Diego Medical Center, 200 West Arbor Drive, Mail Code 8320, San Diego, CA 92103, USA
Mitch Diccianni
- University of California, San Diego Medical Center, 200 West Arbor Drive, Mail Code 8320, San Diego, CA 92103, USA
Bruce M Camitta
- Midwest Children's’ Cancer Center, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Brett P Monia
- Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
Nicholas M Dean
- Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA

Received 19 February 2001; accepted 25 June 2001.

Abstract

We have examined the effects of antisense oligonucleotides to bcl-x on the survival and chemosensitivity of CEM cells, a T-acute lymphoblastic leukemia (T-ALL) cell line. Also, we have measured the levels of Bcl-2, Bcl-x, and Bax in 20 cases of T-ALL. By 18 h after the bcl-x antisense treatment, CEM cells showed over a 75% reduction in the levels of Bcl-xL protein and over 30% decreased viable cell counts compared with cells treated with the control oligonucleotide. The combination of bcl-x antisense plus either dexamethasone or doxorubicin showed either strong synergistic or additive killing of CEM cells, respectively. These findings indicate that bcl-x antisense has cytotoxic activity and increases chemotherapy-induced cell death in CEM cells, a model for T-ALL.

Keywords: Antisense, bcl-2, bcl-x, Drug sensitivity, Glucocorticoid, T-ALL

Abbreviations: T-ALL, T-cell acute lymphoblastic leukemia, FBS, fetal bovine serum, CI, combination index, PBL, peripheral blood lymphocytes, Thy, Thymus