Summary
3′-Deoxy-3′-fluorothymidine (FT), a thymidine analogue highly effective against HIV 1 in vitro was investigated as to its in vitro effect on normal human bone marrow CFU-GM (agar colony assay) and on human peripheral myeloid leukaemic clonogenic cells (CFU-L, colony assay in methylcellulose). For comparison, 3′-azido-3′-deoxythymidine (AZT), structurally related and used in AIDS treatment, was included in the study. Both compounds inhibit the formation of clusters and colonies from bone marrow stem cells with an [IC]50 between 10−6 and 10−5M. In concentrations only 5–10 times lower than the [IC]50, FT begins to stimulate cluster and colony formation. AZT and FT also inhibit the formation of clusters and colonies from CFU-L. Compared to CFU-GM, CFU-L were more sensitive to FT, and a stimulation was not seen. It is concluded that similar side effects on bone marrow could be expected for possible use of FT against AIDS as have been found for AZT and that both compounds are potential candidates for antileukaemic drugs.
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References
Bennet JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1976) Proposals for the classification of the acute leukaemias. FAB Cooperative group. Br J Haematol 33: 451–458
Buick RN, Till JE, Mc Culloch EA (1977) Colony assay for proliferative blast cells circulating in myeloblastic leukaemia. Lancet I: 862–863
Dainiak N, Worthington M, Riordan M, Kreczko S, Goldman L (1988) 3′-Azido-3′deoxythymidine (AZT) inhibits proliferation in-vitro of human haematopoietic progenitor cells. Br J Haematol 69: 299–304
Etzold G, Hintsche R, Kowollik G, Langen P (1971) Nucleoside von Fluorzuckern VI. Synthese und Reaktionen von 3′-Fluor- und 3′-Chlor-3′-Desoxy-Thymidin. Tetrahedron 27: 2463–2472
Ganser A, Greher J, Voelkers B, Staszewski S, Hoelzer D (1988) Azidothymidin in the Treatment of AIDS (Letter to the Editor) N Engl J Med 318: 250–251
Langen P, Graetz H, v Janta-Lipinski M, Weiss H (1978) Effects of 3′-deoxy-3′-fluorothymidine on proliferation kinetics of Ehrlich ascites Tumour cells in vitro (Comparison with other cytostatic drugs). Eur J Cancer 14: 349–354
Lin TS, Prusoff WH (1978) Synthesis and biological activity of several amino analogues of thymidine. J Med Chem 21: 109–112
Matthes E, Lehmann C, Scholz D, Rosenthal HA, Langen P, (1988) Phosphorylation, anti-HIV activity and cytotoxicity of 3′-Fluorothymidine. Biochem Biophys Res Commun 153: 825–831
Minden MD, Buick RN, Mc Culloch EA (1979) Separation of blast cell and T-lymphocyte progenitors in the blood of patients with acute myeloblastic leukaemia. Blood 54: 186–195
Pike BL, Robinson WA (1970) Human bone marrow colony growth in agar-gel. J Cell Physiol 76: 77–84
Richmann DD, Fischl MA, Grieco MH, Gottlieb MS, Volberding PA, Laskin OL, Leedom JM, Groopman JE, Mildvan D, Hirsch MS, Jackson GG, Durack DT, Nusinoff-Lehrman S, the AZT Collaborative Wirkung Group (1987) The Toxicity of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-related Complex. N Engl J Med 317: 192–197
Sommadossi JP, Carlisle R (1987) Toxicity of 3′-azido-3′-deoxythymidine and 9-(1,2-dihydroxy-2-propoxymethyl) guanine for normal human hematopoietic progenitor cells in vitro. Antimicrob Agents Chemother 31: 452–454
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Blau, I.W., Elstner, E., Waechter, M. et al. Sensitivity of CFU-GM from normal human bone marrow and leukaemic clonogenic cells (CFU-L) from blood of patients with myelogenous leukaemia to 3′-deoxy-3′-fluorothymidine in comparison to 3′-azido-3′-deoxythymidine. Blut 59, 455–457 (1989). https://doi.org/10.1007/BF00349067
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DOI: https://doi.org/10.1007/BF00349067