Induction of apoptosis in vivo and in vitro in hairy cell leukemia treated by deoxycoformycin.
The leukemic cells of a patient with hairy cell leukemia were treated in vitro with 2'-deoxycoformycin (dCF), an inhibitor of adenosine deaminase, and deoxyadenosine (dAdo). Following this treatment, viability of the hairy cells progressively declined, and DNA fragmentation was observed. When the patient was treated with 4 mg/m2 dCF intravenously, hairy cells in his peripheral blood rapidly decreased, and a large number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP- biotin nick end-labeling)-positive cells were detected in a bone marrow biopsy specimen. These findings indicate that dCF induced apoptosis of hairy cells both in vivo and in vitro. Furthermore, bcl-2 mRNA was down-regulated by dCF and dAdo in the hairy cells in vitro. Our results suggest the importance of bcl-2 mRNA regulation in apoptotic cell death mediated by dCF in hairy cell leukemia.
Ogawa
K
K
The First Department of Internal Medicine, Fukushima Medical University, Japan.
Shichishima
T
T
Nakamura
N
N
Maruyama
Y
Y
D000368:Aged; D017209:Apoptosis; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D015649:Pentostatin / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D015649:Pentostatin