Intraclonal Heterogeneity in the In Vitro Daunorubicin-Induced Apoptosis in Acute Myeloid Leukemia

Leukemic cells from ten patients with acute myeloid leukemia (AML) were sorted on the basis of in vitro daunorubicin (DNR) uptake. The obtained subpopulations with high and low DNR accumulation were compared with regard to induction of apoptosis, expression of bcl-2 and p53. Heterogeneous induction...

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Bibliographic Details
Published in:Leukemia & lymphoma 1999, Vol.32 (3-4), p.309-316
Main Authors: Palucka, Karolina A., Knaust, Eva, Xu, Dawei, Macnamara, Barbara, Porwit-MacDonald, Anna, Gruber, Astrid, Peterson, Curt, Björkholm, Magnus, Pisa, Pavel
Format: Article
Language:English
Subjects:
Acute Disease
apoptosis
Apoptosis - drug effects
bcl-2
Cell Separation
Clone Cells - drug effects
Clone Cells - pathology
daunorubicin
Daunorubicin - metabolism
Daunorubicin - pharmacology
Drug Resistance, Neoplasm
Humans
leukemia
Leukemia, Myeloid - drug therapy
Leukemia, Myeloid - metabolism
Leukemia, Myeloid - pathology
MEDICIN
Medicin och hälsovetenskap
MEDICINE
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Tumor Cells, Cultured
Tumor Suppressor Protein p53 - biosynthesis
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Summary:Leukemic cells from ten patients with acute myeloid leukemia (AML) were sorted on the basis of in vitro daunorubicin (DNR) uptake. The obtained subpopulations with high and low DNR accumulation were compared with regard to induction of apoptosis, expression of bcl-2 and p53. Heterogeneous induction of apoptosis, confined to subpopulations with high DNR uptake, was observed. The size of the DNR-induced apoptotic fraction (4% to 16%) within a given AML blast population was determined by intracellular drug accumulation and was not related to the level of bcl-2 expression. All tested leukemic samples displayed expression of p53 in a growth promoter orientation, i.e. PAb1620-/PAb240+. In two samples, however, sub-populations expressing a growth suppressor orientation of p53, i.e. PAb1620+/PAb240-, were also present. These subpopulations were confined to high-DNR-uptake fractions and associated with the induction of apoptosis. We conclude that intraclonal heterogeneity in the intracellular drug accumulation and subsequently in DNR-induced apoptosis might allow the selection of inherently drug-resistant AML clones thus contributing to relapse of leukemia.
ISSN:1042-8194
1029-2403
1029-2403
DOI:10.3109/10428199909167391