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Bcr‐Abl kinase promotes cell cycle entry of primary myeloid CML cells in the absence of growth factors
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Personen und Körperschaften: | , , , , , , , |
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Titel: |
Bcr‐Abl kinase promotes cell cycle entry of primary myeloid CML cells in the absence of growth factors |
In: | British Journal of Haematology, 100, 1998, 2, S. 295-303 |
veröffentlicht: |
Wiley
|
Umfang: | 295-303 |
ISSN: |
0007-1048 1365-2141 |
DOI: | 10.1046/j.1365-2141.1998.00564.x |
Zusammenfassung: | <jats:p>Cell cycle control of both immature and differentiated primary myeloid normal and chronic‐phase chronic myeloid leukaemia (CML) cells to growth factor deprivation was studied. CD34<jats:sup>+</jats:sup> cells were cultured in liquid culture. After removal of growth factors for 48 h normal cells were very efficiently arrested with the fraction of cells in S phase reduced by 70.8 ± 6.5% in CD34<jats:sup>+</jats:sup> and 50.5 ± 4.2% in CD34<jats:sup>−</jats:sup> cells. In contrast, a significantly higher proportion of leukaemic cells remained in S phase. The fraction of S‐phase cells was reduced by only 29.3 ± 5.7% in CD34<jats:sup>+</jats:sup> CML cells and 21.2 ± 3.8% in CD34<jats:sup>−</jats:sup> cells. This abnormal negative cell cycle control in leukaemic cells was specific for growth factor deprivation. Reaction to IFN‐α and TNF‐α treatment was identical both in normal and CML cells. Equal quantities of the cytokines TNF‐α, IL‐1α, IL‐1RA and IL‐6 were produced by CML and normal cells. However, production of GM‐CSF, with a median of 11 ± 5 pg/ml, was found only in the supernatants of CML cells. But antibodies to GM‐CSF did not restore growth factor dependence of the leukaemic cells. The defect was completely corrected by the abl‐specific tyrosine kinase inhibitor CGP 57148 without effecting cell cycle control of normal cells. Our results demonstrate a directly Bcr‐Abl‐dependent defective response of both immature and differentiated primary myeloid CML cells to growth factor deprivation.</jats:p> |
Format: | E-Article |
Quelle: | Wiley (CrossRef) |
Sprache: | Englisch |