Cl-IB-MECA inhibits human erythropoiesis.
Candidate drugs are being sought for the suppression of human erythropoiesis. Cl-IB-MECA [2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide] is a derivative of adenosine that inhibits the growth of leukaemic cell lines. To determine the effects of Cl-IB-MECA upon erythropoiesis, studies were performed by using an ex vivo culture system of primary human CD34+ cells. Cl-IB-MECA suppressed erythroblast growth and maturation at doses >/=50 mumol/l through a mechanism of cell cycle inhibition and accumulation of cells in the G1/G0 phase. These findings demonstrate that Cl-IB-MECA inhibits human erythropoiesis, and suggest that further consideration of this drug is warranted for patients with erythrocytosis or polycythemia syndromes.
Bhanu
Natarajan V
NV
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Aerbajinai
Wulin
W
Gantt
Nicole M
NM
Jackson
Edwin K
EK
Goh
Sung-Ho
SH
Terry Lee
Y
Y
Miller
Jeffery L
JL
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004900:Erythroblasts / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D016133:Polymerase Chain Reaction / Q000379:methods; D043684:Receptor, Adenosine A3 / Q000032:analysis; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D003470:Culture Media; D043684:Receptor, Adenosine A3; D004921:Erythropoietin; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide