Comparison of in vitro inhibition of etoposide (VP16) on leukemic and normal myeloid, erythroid clonogenic cells.
We have compared in various clonogenic assays the in vitro sensitivity to etoposide (VP16) of 1) human leukemic precursors (leukemia colony-forming units; L-CFU), 2) normal erythroid progenitors (erythroid burst-forming units; BFU-E, and 3) normal committed myeloid progenitors (granulocyte-macrophage colony-forming units; CFU-GM and more primitive hemopoietic precursors (PPC) that adhere to cultured marrow stromal cells. Bone marrow samples were obtained from 15 normal subjects and 16 leukemic patients: 9 in the acute phase of acute nonlymphoblastic leukemia (ANLL) and 7 in complete remission. VP16 was tested at concentrations ranging from 10(-8) to 10(-3) M. The median recoveries at 10(-3) M VP16 were respectively 0%, 0.5%, 0%, and 0% for leukemic progenitors, CFU-GM from leukemic patients in complete remission, normal CFU-GM, and BFU-E, and 23% for PPC. This indicates that CFU-GM, BFU-E, and L-CFU are highly sensitive to VP16, whereas PPC, more primitive myeloid precursors, are spared. These results suggest that VP16 may be used as an "ex vivo" purging agent for autologous bone marrow.
Lagneaux
L
L
Service de médecine interne, Institut J. Bordet, Brussels, Belgium.
Marie
J P
JP
Delforge
A
A
Socquet
M
M
Thevenin
D
D
Zittoun
R
R
Stryckmans
P
P
D002470:Cell Survival / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology* / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007399:Interphase; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D005047:Etoposide