Apoptosis induction in peripheral leukemia cells by remission induction treatment in vivo: selective depletion and apoptosis in a CD34+ subpopulation of leukemia cells.
In vitro studies demonstrating the induction of programmed cell death by cytotoxic drugs used in anticancer chemotherapy suggested that antileukemic treatment eliminates leukemia cells by apoptosis. We therefore analyzed apoptosis induction and activation of apoptosis signaling molecules in patients receiving remission induction treatment for AML and ALL during the initial phase of leukemia cell reduction. A coexistence of distinct populations of CD34(+) and CD34(-) leukemia cells could be identified. During chemotherapy, CD34(+) leukemia cells were more rapidly depleted than CD34(-) cells. Furthermore, a significant increase in leukemia cell apoptosis ex vivo was detected in CD34(+) cells, while no such increase was observed in the CD34(-) subpopulation, suggesting that CD34(+) leukemia cells are the main targets for apoptosis induction through antileukemic treatment. No alterations in Bax and Bcl-2 expression were found during in vivo chemotherapy, and CD95 expression and sensitivity remained low, indicating the induction of apoptosis independent of the CD95 system or regulation of protein levels of Bax and Bcl-2. The data suggest that analysis of leukemia cell subpopulations is required for further identification of apoptosis signaling molecules relevant for response to treatment and assessment of drug efficacy in vivo and in vitro.
Stahnke
K
K
University Children's Hospital, Ulm, Germany.
Eckhoff
S
S
Mohr
A
A
Meyer
L H
LH
Debatin
K-M
KM
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008212:Lymphocyte Depletion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012074:Remission Induction; D016896:Treatment Outcome; D019014:fas Receptor / Q000097:blood*
D015703:Antigens, CD; D018952:Antigens, CD34; D019014:fas Receptor; D003561:Cytarabine; D005047:Etoposide; D015255:Idarubicin