Factors affecting bryostatin 1-enhanced 2-CdA cytotoxicity in resistant B-cell chronic lymphocytic leukemia

Beck,Frances W.J.; Eilender,Davi S.; Dandashi,Mahmoud H.; Siddiq,Fauzia; Snell,Diane C.; Godmere,Michele A.; Al-Katib,Ayad M.; Mohammad,Ramzi M.

doi:10.3892/ijmm.14.1.113

October 2004 Volume 14 Issue 1

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October 2004 Volume 14 Issue 1

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Article

Factors affecting bryostatin 1-enhanced 2-CdA cytotoxicity in resistant B-cell chronic lymphocytic leukemia

Authors:
- Frances W.J. Beck
- Davi S. Eilender
- Mahmoud H. Dandashi
- Fauzia Siddiq
- Diane C. Snell
- Michele A. Godmere
- Ayad M. Al-Katib
- Ramzi M. Mohammad
View Affiliations / Copyright

Affiliations: Wayne State University School of Medicine, 421 E. Canfield, Detroit, MI 48201, USA. fwbeck@med.wayne.edu or drfranwjbeck@hotmail.com
Pages: 113-119
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Published online on: October 1, 2004

https://doi.org/10.3892/ijmm.14.1.113
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Abstract

Pre-treatment with bryostatin 1 (bryo) has been shown to potentiate the efficacy of (2-chloro-2-deoxyadenosine, cladribine, 2-CdA) in B-cell chronic lymphocytic leukemia (B-CLL) by increasing the ratio of deoxycytidine kinase (dCK) to 5'-nucleotidase (5'-NT) activity. The bryo-induced increase in dCK/5'-NT activity alone has not been a conclusive indication of final clinical outcome. Therefore, we used an ex vivo assay to investigate factors which may affect the bryo-induced enhancement of 2-CdA efficacy in B-CLL patient-derived samples. Bryo-induced increase in dCK/5'-NT was inversely associated with Rai stage CLL (r=−0.86). Increased dCK/5'-NT activity was not correlated with increased efficacy (cell death) or percentage of cellular [8-3H]-2-CdA converted to [8-3H]-2-CdATP ex vivo. Bryo pre-treatment increased the cellular uptake of [8-3H]-2-CdA and incorporation of [8-3H]-2-CdA metabolites into the DNA fraction. Cell death from 2-CdA was inversely correlated with bryo-induced activity of the DNA repair enzyme, DNA-PKcs, (r=−0.77). Thus, the ability of B-CLL to repair damaged DNA may be a more important predictor of the response to bryo/2-CdA and eventual clinical outcome than dCK/5'-NT activity. Additional CLL patients under bryo-2-CdA therapy are needed to verify these important observations.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Factors affecting bryostatin 1-enhanced 2-CdA cytotoxicity in resistant B-cell chronic lymphocytic leukemia

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