Effects of recombinant human tumor necrosis factor on the self-renewal capacity of leukemia blast progenitors in acute myeloblastic leukemia.
The effects of human recombinant tumor necrosis factor type alpha (rTNF alpha) on the blast progenitors from 14 acute myeloblastic leukemia (AML) patients and 1 chronic myelogenous leukemia patient in blastic crisis were studied in methylcellulose and suspension cultures. Blast progenitors renew themselves and/or undergo terminal divisions. Plating efficiency of primary colony formation (PE1) in methylcellulose, which is considered to reflect the terminal divisions of blast progenitors, was suppressed by rTFN alpha in a dose-dependent manner in all cases. Plating efficiency of secondary colony formation (PE2) and the recovery of clonogenic cells in suspension culture, which are considered to reflect the self-renewal capacity of blast progenitors, were also suppressed by rTNF alpha in a dose-dependent manner in almost all cases. rTNF alpha also inhibited both PE2 and clonogenic cells in suspension culture, even in relapsed AML patients who were very refractory to intensive chemotherapies. The results demonstrate that rTNF alpha inhibits not only terminal divisions but also the self-renewal capacity of leukemic blast progenitors. The finding that rTNF alpha suppressed the self-renewal capacity of leukemic blast progenitors proposes the utility of rTNF alpha to AML therapy.
First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
K
K
Nagata
S
S
Tohda
T
T
Suzuki
N
N
Nara
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000473:pathology* / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011994:Recombinant Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000627:therapeutic use
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha