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

  • Published online on: October 1, 2004     https://doi.org/10.3892/ijmm.14.1.113
  • Pages: 113-119
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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.

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October 2004
Volume 14 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Beck FW, Eilender DS, Dandashi MH, Siddiq F, Snell DC, Godmere MA, Al-Katib AM and Mohammad RM: Factors affecting bryostatin 1-enhanced 2-CdA cytotoxicity in resistant B-cell chronic lymphocytic leukemia. Int J Mol Med 14: 113-119, 2004
APA
Beck, F.W., Eilender, D.S., Dandashi, M.H., Siddiq, F., Snell, D.C., Godmere, M.A. ... Mohammad, R.M. (2004). Factors affecting bryostatin 1-enhanced 2-CdA cytotoxicity in resistant B-cell chronic lymphocytic leukemia. International Journal of Molecular Medicine, 14, 113-119. https://doi.org/10.3892/ijmm.14.1.113
MLA
Beck, F. W., Eilender, D. S., Dandashi, M. H., Siddiq, F., Snell, D. C., Godmere, M. A., Al-Katib, A. M., Mohammad, R. M."Factors affecting bryostatin 1-enhanced 2-CdA cytotoxicity in resistant B-cell chronic lymphocytic leukemia". International Journal of Molecular Medicine 14.1 (2004): 113-119.
Chicago
Beck, F. W., Eilender, D. S., Dandashi, M. H., Siddiq, F., Snell, D. C., Godmere, M. A., Al-Katib, A. M., Mohammad, R. M."Factors affecting bryostatin 1-enhanced 2-CdA cytotoxicity in resistant B-cell chronic lymphocytic leukemia". International Journal of Molecular Medicine 14, no. 1 (2004): 113-119. https://doi.org/10.3892/ijmm.14.1.113