CD14+ peripheral blood mononuclear cells from chronic myeloid leukemia and normal donors are inhibitory to short- and long-term cultured colony-forming cells
Monocyte-induced cell-cytotoxicity has been implicated in the mechanism of suppression of normal haematopoietic progenitors in chronic myeloid leukemia (CML). We examined here the in vitro effect of CML-derived and normal peripheral blood (PB) monocytes on short- and long-term cultured haematopoieti...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
11 February 2000
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| In: |
Leukemia research
Year: 2000, Volume: 24, Issue: 3, Pages: 217-231 |
| ISSN: | 1873-5835 |
| DOI: | 10.1016/S0145-2126(99)00171-X |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S0145-2126(99)00171-X Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S014521269900171X 
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| Author Notes: | Beate Heissig, Günther Pasternak, Susanne Hörner, Rainer Schwerdtfeger, Siegfried Rossol, Rüdiger Hehlmann |
| Summary: | Monocyte-induced cell-cytotoxicity has been implicated in the mechanism of suppression of normal haematopoietic progenitors in chronic myeloid leukemia (CML). We examined here the in vitro effect of CML-derived and normal peripheral blood (PB) monocytes on short- and long-term cultured haematopoietic progenitor cells. Short-term coculture (5 days) of CML or normal monocytes with CML or normal peripheral blood mononuclear cells (PBMNC)/CD34+ cells as targets resulted in a significant inhibition of colony-forming cell (CFC) growth. Coculture conditioned medium (CCM) from 5-days cocultures of normal or CML CD14+ monocytes with CD34+ cells were likewise inhibitory to CFC. In 5-week long-term cocultures of monocytes in direct contact with normal bone marrow (BM) progenitors, CML monocytes reduced the proportion of long-term cultured CFC (LTC-CFC) significantly to 52% of the controls, while normal monocytes had a less pronounced inhibitory effect (89% of the controls) on LTC-CFC. Reduction of LTC-CFC was great when CML monocytes and target cells were separated by a transwell membrane as compared to control cultures in the absence of CD14+ cells (53.5 vs. 9%). CCM from 5-week cocultures of normal or CML CD14+ monocytes with CD34+ progenitors from bone marrow (BM) cells were also inhibitory to CFC. No difference in cytokine levels for TNF-α, IFN-γ, G-CSF, IL-10, IL-6 was detectable between CML CD14+ CCM and control CCM derived from short- and long-term cocultures. Our results suggest that CML monocytes may play a role in the inhibition of normal haematopoiesis through a yet not defined soluble factor supporting the expansion of the malignant clone in CML. |
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| Item Description: | Gesehen am 19.05.2022 Im Titel ist das Pluszeichen hochgestellt |
| Physical Description: | Online Resource |
| ISSN: | 1873-5835 |
| DOI: | 10.1016/S0145-2126(99)00171-X |