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Primary proliferating immature myeloid cells from CML patients are not resistant to induction of apoptosis by DNA damage and growth factor withdrawal
Author(s) -
Albrecht Tarja,
Schwab Renate,
Henkes Martin,
Peschel Christian,
Huber Christoph,
Aulitzky Walter E.
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1934.x
Subject(s) - apoptosis , biology , haematopoiesis , terminal deoxynucleotidyl transferase , dna damage , microbiology and biotechnology , flow cytometry , growth factor , programmed cell death , cancer research , immunology , andrology , stem cell , medicine , dna , receptor , tunel assay , biochemistry
Induction of apoptosis by growth factor deprivation or gamma‐irradiation‐induced DNA damage was directly studied in proliferating primary haemopoietic cells derived from CD34‐positive cells of 13 CML patients and 12 normal controls. CD34‐positive cells were cultured in the presence of appropriate concentrations of SCF and G‐CSF for 5–7 d. After gamma irradiation with 500 rad or growth factor deprivation, the fraction of apoptotic cells was assessed by two independent methods applying either measurement of cells incorporating FITC‐labelled dUTP by terminal transferase or assessment of the fraction of cells with a less than 2N DNA content in flow cytometry. Proliferating CML cells were not resistant to the induction of apoptosis either after gamma irradiation or subsequent to growth factor deprivation. A similar fraction of normal and CML cells underwent apoptosis 48 h after withdrawal of growth factors. CML cells displayed an increased susceptibility to induction of apoptosis after DNA damage. A significantly higher proportion of apoptotic cells were detected in samples derived from CML patients after irradiation with 0.5 Gy. These results, in conjunction with conflicting observations by other investigators, on the induction of apoptosis by gamma irradiation in various bcr‐abl positive cells, suggest that bcr‐abl‐dependent effects on apoptosis strongly depend on the cells used. Our observations in CML cells derived exclusively from newly diagnosed CML patients demonstrate that bcr‐abl expression per se is not sufficient to induce resistance to apoptosis.