Leukemia-induced bone marrow depression: Effects of gangliosides on erythroid cell production

Bone marrow depression is a common feature in hemato logical malignancies o r other bone marrow-involving cancers. The mechanism of this hemopoietic su ppression resulting in pancytopenia and especially anemia has not been eluc idated. Gangliosides can be shed by cancer cells. Therefore, we investigate d the effects of exogenously added gangliosides on erythropoiesis in a huma n and murine in vitro system. A dose-dependent inhibition of murine colony- forming-unit-erythroid (CFU-E) and burst-forming unit-erythroid (BFU-E) col ony growth was observed. Furthermore the maturation of BFU-Es into CFU-Es w as inhibited. The inhibition by gangliosides was not abolished by increasin g the dose of erythropoietin (10 U/ml). FACS-analysis studies with human CD 34(+) cells cultured with gangliosides (GM3), erythropoietin (EPO) and stem cell factor (SCF) demonstrated a strong inhibition on cell growth. This re sulted in a significantly higher percentage of immature cells (CD34(+)/GpA( -), 24% vs, 3%), and a lower percentage of mature erythroid cells (CD34(-)/ GpA(+), 36% vs. 89%). Under these circumstances the effects on erythroid ce ll growth were much higher than on other cell lineages. The inhibitory effe ct of gangliosides isolated from acute lymphoblastic leukemic patients on i n vitro erythropoiesis suggests that in vivo hemopoietic suppression might have its origin in the gangliosides present and probably shed by the malign ant cells in the microenvironment and plasma. Our results show that ganglio sides inhibit erythropoiesis in vitro at several stages of development, by a mechanism involving modulation of the maturation of erythroid cells. (C) 1999 Wiley-Liss, Inc.