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The cladribine conundrum: deciphering the drug's mechanism of action

, ScD (Professor) & , PhD (Vice President and Scientific Director)
Pages 75-81 | Published online: 07 Dec 2009

Bibliography

  • Fanta PT, Saven A. Hairy cell leukemia. Cancer Treat Res 2008;142:193-209
  • Greyz N, Saven A. Cladribine: from the bench to the bedside–focus on hairy cell leukemia. Expert Rev Anticancer Ther 2004;4:745-57
  • Krance RA, Hurwitz CA, Head DR, Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases. J Clin Oncol 2001;19:2804-11
  • Robak T. Therapy of chronic lymphocytic leukaemia with purine nucleoside analogues: facts and controversies. Drugs Aging 2005;22:983-1012
  • Tobinai K, Watanabe T, Tanimoto K, Phase I/II and pharmacokinetic study of cladribine with 2-h infusion in Japanese patients with relapsed indolent B-cell lymphoma mostly pretreated with rituximab. Cancer Sci 2009;100:1344-50
  • Tondini C, Balzarotti M, Rampinelli I, Fludarabine and cladribine in relapsed/refractory low-grade non-hodgkin's lymphoma: a phase II randomized study. Ann Oncol 2000;11:231-3
  • Leist TP, Vermersch P. The potential role for cladribine in the treatment of multiple sclerosis: clinical experience and development of an oral tablet formulation. Curr Med Res Opin 2007;23:2667-76
  • Linker RA, Kieseier BC, Gold R. Identification and development of new therapeutics for multiple sclerosis. Trends Pharmacol Sci 2008;29:558-65
  • Martinez-Rodriguez JE, Cadavid D, Wolansky LJ, Cladribine in aggressive forms of multiple sclerosis. Eur J Neurol 2007;14:686-9
  • Rubnitz JE, Crews KR, Pounds S, Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St Jude AML97 trial. Leukemia 2009;23:1410-16
  • Wierzbowska A, Robak T, Pluta A, Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol 2008;80:115-26
  • Korycka A, Robak T. The influence of imatinib mesylate (STI571) used alone or in combination with purine nucleoside analogues on the normal and chronic myelogenous leukaemia progenitor cells in vitro. Leuk Lymphoma 2003;44:1549-55
  • Robak T. Purine nucleoside analogues in the treatment of myleoid leukemias. Leuk Lymphoma 2003;44:391-409
  • Inwards DJ, Fishkin PA, Hillman DW, Long-term results of the treatment of patients with mantle cell lymphoma with cladribine (2-CDA) alone (95-80-53) or 2-CDA and rituximab (N0189) in the North Central Cancer Treatment Group. Cancer 2008;113:108-16
  • Robak T, Smolewski P, Cebula B, Rituximab plus cladribine with or without cyclophosphamide in patients with relapsed or refractory chronic lymphocytic leukemia. Eur J Haematol 2007;79:107-13
  • Walker AR, Komrokji RS, Ifthikharuddin J, Phase I study of cladribine, cytarabine (Ara-C), granulocyte colony stimulating factor (G-CSF) (CLAG Regimen) and simultaneous escalating doses of imatinib mesylate (Gleevec) in relapsed/refractory AML. Leuk Res 2008;32:1830-6
  • Else M, Osuji N, Forconi F, The role of rituximab in combination with pentostatin or cladribine for the treatment of recurrent/refractory hairy cell leukemia. Cancer 2007;110:2240-7
  • Parker WB, Bapat AR, Shen JX, Interaction of 2-halogenated dATP analogs (F, Cl, and Br) with human DNA polymerases, DNA primase, and ribonucleotide reductase. Mol Pharmacol 1988;34:485-91
  • Carson DA, Wasson DB, Kaye J, Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo. Proc Natl Acad Sci USA 1980;77:6865-9
  • Griffig J, Koob R, Blakley RL. Mechanisms of inhibition of DNA synthesis by 2-chlorodeoxyadenosine in human lymphoblastic cells. Cancer Res 1989;49:6923-8
  • Fyrberg A, Albertioni F, Lotfi K. RNAi depletion of deoxycytidine and deoxyguanosine kinase in human leukemic CEM cells. Nucleosides Nucleotides Nucleic Acids 2008;27:712-19
  • Lotfi K, Juliusson G, Albertioni F. Pharmacological basis for cladribine resistance. Leuk Lymphoma 2003;44:1705-12
  • Hentosh P, Koob R, Blakley RL. Incorporation of 2-halogeno-2′-deoxyadenosine 5-triphosphates into DNA during replication by human polymerases alpha and beta. J Biol Chem 1990;265:4033-40
  • Yuh SH, Tibudan M, Hentosh P. Analysis of 2-chloro-2′-deoxyadenosine incorporation into cellular DNA by quantitative polymerase chain reaction. Anal Biochem 1998;262:1-8
  • Hartman WR, Hentosh P. The antileukemia drug 2-chloro-2′-deoxyadenosine: an intrinsic transcriptional antagonist. Mol Pharmacol 2004;65:227-34
  • Seto S, Carrera CJ, Kubota M, Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes. J Clin Invest 1985;75:377-83
  • Mellon I, Bohr VA, Smith CA, Preferential DNA repair of an active gene in human cells. Proc Natl Acad Sci USA 1986;83:8878-82
  • Chen LS, Plunkett W, Gandhi V. Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues. Leuk Res 2008;32:1573-81
  • Spurgeon S, Yu M, Phillips JD, Cladribine: not just another purine analogue? Expert Opin Investig Drugs 2009;18:1169-81
  • Carson DA, Wasson DB, Taetle R, Specific toxicity of 2-chlorodeoxyadenosine toward resting and proliferating human lymphocytes. Blood 1983;62:737-43
  • Carson DA, Wasson DB, Esparza LM, Oral antilymphocyte activity and induction of apoptosis by 2-chloro-2′-arabino-fluoro- 2′-deoxyadenosine. Proc Natl Acad Sci USA 1992;89:2970-4
  • Huang MC, Ashmun RA, Avery TL, Effects of cytotoxicity of 2-chloro-2′-deoxyadenosine and 2-bromo-2′-deoxyadenosine on cell growth, clonogenicity, DNA synthesis, and cell cycle kinetics. Cancer Res 1986;46:2362-8
  • Kearns CM, Blakley RL, Santana VM, Pharmacokinetics of cladribine (2-chlorodeoxyadenosine) in children with acute leukemia. Cancer Res 1994;54:1235-9
  • Liliemark J, Juliusson G. On the pharmacokinetics of 2-chloro-2′-deoxyadenosine in humans. Cancer Res 1991;51:5570-2
  • Beutler E. Cladribine (2-chlorodeoxyadenosine). Lancet 1992;340:952-6
  • Liliemark J, Juliusson G. Cellular pharmacokinetics of 2-chloro-2′-deoxyadenosine nucleotides: comparison of intermittent and continuous intravenous infusion and subcutaneous and oral administration in leukemia patients. Clin Cancer Res 1995;1:385-90
  • Albertioni F, Lindemalm S, Reichelova V, Pharmacokinetics of cladribine in plasma and its 5′-monophosphate and 5′-triphosphate in leukemic cells of patients with chronic lymphocytic leukemia. Clin Cancer Res 1998;4:653-8
  • Robertson LE, Chubb S, Meyn RE, Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2′-deoxyadenosine and 9-beta-D-arabinosyl-2-fluoroadenine. Blood 1993;81:143-50
  • Zinzani PL, Tosi P, Visani G, Apoptosis induction with three nucleoside analogs on freshly isolated B-chronic lymphocytic leukemia cells. Am J Hematol 1994;47:301-6
  • Nomura Y, Inanami O, Takahashi K, 2-Chloro-2′-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4. Leukemia 2000;14:299-306
  • Genini D, Budihardjo I, Plunkett W, Nucleotide requirements for the in vitro activation of the apoptosis protein-activating factor-1-mediated caspase pathway. J Biol Chem 2000;275:29-34
  • Leoni LM, Chao Q, Cottam HB, Induction of an apoptotic program in cell-free extracts by 2-chloro-2′-deoxyadenosine 5′-triphosphate and cytochrome c. Proc Natl Acad Sci USA 1998;95:9567-71
  • Gandhi V, Kemena A, Keating MJ, Cellular pharmacology of fludarabine triphosphate in chronic lymphocytic leukemia cells during fludarabine therapy. Leuk Lymphoma 1993;10:49-56
  • Genini D, Adachi S, Chao Q, Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria. Blood 2000;96:3537-43
  • Cardoen S, Van Den Neste E, Smal C, Resistance to 2-chloro-2′-deoxyadenosine of the human B-cell leukemia cell line EHEB. Clin Cancer Res 2001;7:3559-66
  • Conrad DM, Robichaud MR, Mader JS, 2-Chloro-2′-deoxyadenosine-induced apoptosis in T leukemia cells is mediated via a caspase-3-dependent mitochondrial feedback amplification loop. Int J Oncol 2008;32:1325-33
  • Marzo I, Perez-Galan P, Giraldo P, Cladribine induces apoptosis in human leukaemia cells by caspase-dependent and -independent pathways acting on mitochondria. Biochem J 2001;359:537-46
  • Smal C, Lisart S, Maerevoet M, Pharmacological inhibition of the MAPK/ERK pathway increases sensitivity to 2-chloro-2′-deoxyadenosine (CdA) in the B-cell leukemia cell line EHEB. Biochem Pharmacol 2007;73:351-8
  • Gewirtz DA, Holt SE, Elmore LW. Accelerated senescence: an emerging role in tumor cell response to chemotherapy and radiation. Biochem Pharmacol 2008;76:947-57
  • Herr I, Debatin KM. Cellular stress response and apoptosis in cancer therapy. Blood 2001;98:2603-14
  • Rebbaa A, Zheng X, Chou PM, Caspase inhibition switches doxorubicin-induced apoptosis to senescence. Oncogene 2003;22:2805-11
  • Schmitt CA, Fridman JS, Yang M, A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 2002;109:335-46
  • Chandra J, Mansson E, Gogvadze V, Resistance of leukemic cells to 2-chlorodeoxyadenosine is due to a lack of calcium-dependent cytochrome c release. Blood 2002;99:655-63
  • Hentosh P, Tibudan M. 2-Chloro-2′-deoxyadenosine, an antileukemic drug, has an early effect on cellular mitochondrial function. Mol Pharmacol 1997;51:613-19
  • Castejon R, Vargas JA, Briz M, Induction of apoptosis by 2-chlorodeoxyadenosine in B cell chronic lymphocytic leukemia. Leukemia 1997;11:1253-7
  • Stachnik K, Grieb P, Skierski JS. Cytotoxic effects of cladribine and tezacitabine toward HL-60. Acta Biochim Pol 2005;52:561-5
  • Lee MW, Kim WJ, Beardsley DI, N-methyl-N'-nitro-N-nitrosoguanidine activates multiple cell death mechanisms in human fibroblasts. DNA Cell Biol 2007;26:683-94
  • Stephenson LM, Miller BC, Ng A, Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes. Autophagy 2009;5:625-35
  • Ideo A, Hashimoto K, Shimada J, Type of cell death induced by alpha-trifluoromethyl acyloins in oral squamous cell carcinoma. Anticancer Res 2009;29:175-81
  • Pettitt AR, Cawley JC. Caspases influence the mode but not the extent of cell death induced by purine analogues in chronic lymphocytic leukaemia. Br J Haematol 2000;109:800-4
  • Laane E, Tamm KP, Buentke E, Cell death induced by dexamethasone in lymphoid leukemia is mediated through initiation of autophagy. Cell Death Differ 2009;16:1018-29
  • Chen YJ, Huang WP, Yang YC, Platonin induces autophagy-associated cell death in human leukemia cells. Autophagy 2009;5:173-83
  • Crazzolara R, Bradstock KF, Bendall LJ. RAD001 (Everolimus) induces autophagy in acute lymphoblastic leukemia. Autophagy 2009;5:727-8
  • Ghavami S, Asoodeh A, Klonisch T, Brevinin-2R(1) semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway. J Cell Mol Med 2008;12:1005-22
  • Yokoyama T, Miyazawa K, Naito M, Vitamin K2 induces autophagy and apoptosis simultaneously in leukemia cells. Autophagy 2008;4:629-40

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