The gp 130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti-proliferative effect of dexamethasone on human myeloma cells

International audienceIn order to understand the mechanisms supporting steroid escape in patients with multiple myeloma (MM), three IL-6 autocrine human myeloma cell lines, LP1, OPM2 and L363, have been treated with dexamethasone in the presence or absence of cytokines belonging to the gp 130 family: IL-6, LIF, OSM and IL-11. With pharmacological doses of dexamethasone, a dramatic growth arrest was observed in all the cell lines. IL-6 completely reversed this inhibition. Of note, this IL-6 induced reversion was still seen with very low amounts of IL-6 (12 pg/ml). Finally, whereas LIF and OSM had clear growth-promoting effects on OPM2 only, both cytokines (but not IL-11) reversed the dexamethasone-induced growth arrest in all the cell lines. Therefore the high levels of IL-6 (ng/ml) observed in the MM intermediate milieu and the putative presence of LIF and OSM can easily counteract the effects of dexamethasone in vivo

The gp 130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti-proliferative effect of dexamethasone on human myeloma cells

International audienceIn order to understand the mechanisms supporting steroid escape in patients with multiple myeloma (MM), three IL-6 autocrine human myeloma cell lines, LP1, OPM2 and L363, have been treated with dexamethasone in the presence or absence of cytokines belonging to the gp 130 family: IL-6, LIF, OSM and IL-11. With pharmacological doses of dexamethasone, a dramatic growth arrest was observed in all the cell lines. IL-6 completely reversed this inhibition. Of note, this IL-6 induced reversion was still seen with very low amounts of IL-6 (12 pg/ml). Finally, whereas LIF and OSM had clear growth-promoting effects on OPM2 only, both cytokines (but not IL-11) reversed the dexamethasone-induced growth arrest in all the cell lines. Therefore the high levels of IL-6 (ng/ml) observed in the MM intermediate milieu and the putative presence of LIF and OSM can easily counteract the effects of dexamethasone in vivo

Differential expression of Bcl-2 in human plasma cell disorders according to proliferation status and malignancy

International audienceMultiple myeloma (MM) is a malignancy characterized by a very slow proliferation of malignant plasma cells leading to their accumulation within the bone marrow. This suggests that resistance to apoptosis may play a critical role both in the pathogenesis and resistance to treatment of MM. Bcl-2 is a key protein for the regulation of apoptosis. However, it has been shown that this protein also regulates the state of proliferation. In the current study, we show that malignant plasma cells from both the bone marrow and peripheral blood express high levels of Bcl-2 and are slowly proliferating cells. In contrast, myeloma cells from extramedullary sites (ie pleural effusion, ascitis, mammary and gastric plasmacytoma) express Bcl-2 weakly while being highly proliferative. Normal non-dividing bone marrow plasma cells express high levels of Bcl-2 protein. In contrast, four highly proliferative reactive plasmacytosis express weak levels of Bcl-2. We conclude that there is an inverse correlation between Bcl-2 expression and the proliferation rate of both normal and malignant plasma cells. These data may be explained by the double function of Bcl-2, ie its well known function as an anti-apoptotic molecule and its intriguing function as an inhibitory molecule of cell proliferation

Differential expression of Bcl-2 in human plasma cell disorders according to proliferation status and malignancy

International audienceMultiple myeloma (MM) is a malignancy characterized by a very slow proliferation of malignant plasma cells leading to their accumulation within the bone marrow. This suggests that resistance to apoptosis may play a critical role both in the pathogenesis and resistance to treatment of MM. Bcl-2 is a key protein for the regulation of apoptosis. However, it has been shown that this protein also regulates the state of proliferation. In the current study, we show that malignant plasma cells from both the bone marrow and peripheral blood express high levels of Bcl-2 and are slowly proliferating cells. In contrast, myeloma cells from extramedullary sites (ie pleural effusion, ascitis, mammary and gastric plasmacytoma) express Bcl-2 weakly while being highly proliferative. Normal non-dividing bone marrow plasma cells express high levels of Bcl-2 protein. In contrast, four highly proliferative reactive plasmacytosis express weak levels of Bcl-2. We conclude that there is an inverse correlation between Bcl-2 expression and the proliferation rate of both normal and malignant plasma cells. These data may be explained by the double function of Bcl-2, ie its well known function as an anti-apoptotic molecule and its intriguing function as an inhibitory molecule of cell proliferation

A phase I/II feasibility vaccine study by autologous leukemic apoptotic corpse-pulsed dendritic cells for elderly AML patients

International audienceThis was a phase I/II study testing the feasibility of a vaccine by autologous leukemic apoptotic corpse-pulsed dendritic cells (DC) in elderly acute myeloid leukemia (AML) patients in first or second complete remission. Pulsed DC were administered at doses of 9 × 106 subcutaneously (1 mL) and 1 × 106 intra-dermally (0.1 mL). Five doses of vaccine were planned on days +1 + 7 + 14 + 21 and +35. Five DC-vaccines were produced and injected for all five patients included in the study. No severe adverse event was documented. Larger Phase 2 studies are now required to precise the role of DC-vaccines with leukemic apoptotic bodies in older as well as younger AML populations