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 leukemi a (CML). We examined here the in vitro effect of CML-derived and normal per ipheral blood (PB) monocytes on short- and long-term cultured haematopoieti c progenitor cells. Short-term coculture (5 days) of CML or normal monocyte s with CML or normal peripheral blood mononuclear cells (PBMNC)/CD34(+) cel ls as targets resulted in a significant inhibition of colony-forming cell ( CFC) growth. Coculture conditioned medium (CCM) from 5-days cocultures of n ormal 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 o f long-term cultured CFC (LTC-CFC) significantly to 52% of the controls, wh ile normal monocytes had a less pronounced inhibitory effect (89% of the co ntrols) on LTC-CFC. Reduction of LTC-CFC was great when CML monocytes and t arget cells were separated by a transwell membrane as compared to control c ultures in the absence of CD14(+) cells (53.5 vs. 9%). CCM from 5-week cocu ltures of normal or CML CD14(+) monocytes with CD34(+) progenitors from bon e marrow (BM) cells were also inhibitory to CFC. No difference in cytokine levels for TNF-alpha, IFN-gamma, G-CSF, IL-10, IL-6 was detectable between CML CD14(+) CCM and control CCM derived from short- and long-term coculture s. Our results suggest that CML monocytes may play a role in the inhibition of normal haematopoiesis through a yet not defined soluble factor supporti ng the expansion of the malignant clone in CML. (C) 2000 Elsevier Science L td. All rights reserved.