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.
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(-5)M. 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 anti-leukaemic drugs.
Blau
I W
IW
Clinic of Internal Medicine, Department of Haematology, Charite, Humboldt University, Berlin.
Elstner
E
E
Waechter
M
M
Ihle
R
R
von Janta-Lipinski
M
M
Langen
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D015224:Dideoxynucleosides / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D015224:Dideoxynucleosides; D015215:Zidovudine; C002854:alovudine