Old and new insights into the mechanisms of action of two nucleoside analogs active in lymphoid malignancies: fludarabine and cladribine (Review)

  • Authors:
    • Eric Van Den Neste
    • Sabine Cardoen
    • Fritz Offner
    • Françoise Bontemps
  • View Affiliations

  • Published online on: October 1, 2005     https://doi.org/10.3892/ijo.27.4.1113
  • Pages: 1113-1124
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Abstract

This review focuses on two chemotherapeutic agents belonging to the family of purine analogs, 9-β-D-arabinosyl-2-fluoroadenine-5'-monophosphate (F-ara-AMP, fludarabine), which is the soluble form of F-ara-A, and 2-chloro-2'-deoxyadenosine (CdA, cladribine). Both compounds display remarkable activity in malignancies arising from the clonal expansion of lymphocytes, and particularly in B-cell chronic lymphocytic leukemia (B-CLL). These analogs are prodrugs that must be converted into their respective nucleotides as an essential requirement for cytotoxicity. Triphosphate analogs inhibit various processes involved in DNA and RNA synthesis. Moreover, the effect of nucleoside analogs in leukemic cells may involve modulation of apoptosis pathways, cell-cycle control, or signal transduction pathways. These findings are of crucial importance because alterations in these pathways may be involved in leukemic cell resistance toward nucleoside analogs and, hence, constitute new molecular targets to sensitize leukemic cells to these drugs.

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October 2005
Volume 27 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Van Den Neste E, Cardoen S, Offner F and Bontemps F: Old and new insights into the mechanisms of action of two nucleoside analogs active in lymphoid malignancies: fludarabine and cladribine (Review). Int J Oncol 27: 1113-1124, 2005
APA
Van Den Neste, E., Cardoen, S., Offner, F., & Bontemps, F. (2005). Old and new insights into the mechanisms of action of two nucleoside analogs active in lymphoid malignancies: fludarabine and cladribine (Review). International Journal of Oncology, 27, 1113-1124. https://doi.org/10.3892/ijo.27.4.1113
MLA
Van Den Neste, E., Cardoen, S., Offner, F., Bontemps, F."Old and new insights into the mechanisms of action of two nucleoside analogs active in lymphoid malignancies: fludarabine and cladribine (Review)". International Journal of Oncology 27.4 (2005): 1113-1124.
Chicago
Van Den Neste, E., Cardoen, S., Offner, F., Bontemps, F."Old and new insights into the mechanisms of action of two nucleoside analogs active in lymphoid malignancies: fludarabine and cladribine (Review)". International Journal of Oncology 27, no. 4 (2005): 1113-1124. https://doi.org/10.3892/ijo.27.4.1113