Abstract
2-Chloro-2′-deoxyadenosine (CdA) is a congener of deoxyadenosine that is resistant to adenosine deaminase. Rationale for the development of CdA as an immunosuppressive and antineoplastic agent derives from the lymphocytotoxicity of elevated plasma deoxyadenosine in congenital deficiency of adenosine deaminase1. Recent clinical trials have documented promising efficacy of CdA in the treatment of chronic B-cell and T-cell lymphoid malignancies, notably chronic lymphocytic leukemia (CLL) and hairy cell leukemia2,3. Among nucleoside antimetabolites, CdA is uniquely toxic to non-dividing lymphocytes, as well as to most proliferating T-lymphoblasts4. Surprisingly, mature blood monocytes are also lysed by CdA at the nanomolar concentrations readily achieved by continuous infusion in vivo5. In both non-dividing lymphocytes and monocytes, CdA causes the prompt accumulation of DNA strand breaks, with subsequent NAD depletion, inhibition of RNA synthesis, and eventual cell lysis5,6.
Keywords
- Chronic Lymphocytic Leukemia
- Adenosine Deaminase
- Hairy Cell Leukemia2
- Chronic Lymphocytic Leukemia Cell
- Deoxycytidine Kinase
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Carrera, C.J., Piro, L.D., Saven, A., Beutler, E., Terai, C., Carson, D.A. (1991). 2-Chlorodeoxyadenosine Chemotherapy Triggers Programmed Cell Death in Normal and Malignant Lymphocytes. In: Harkness, R.A., Elion, G.B., Zöllner, N. (eds) Purine and Pyrimidine Metabolism in Man VII. Advances in Experimental Medicine and Biology, vol 309A. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-2638-8_3
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DOI: https://doi.org/10.1007/978-1-4899-2638-8_3
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