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Polysaccharide is one of main components in Polygonatum sibiricum (PS), which is an herbal medicine widely used in East Asia. Polysaccharides from Polygonatum sibiricum has been shown to exhibit multiple biological activities, such as anti-diabetes, anti-inflammation, antioxidant, immunity modulation, and anticancer. Since hematopoietic system is one of determinant factors in cancer control, we here explored the effect of polysaccharide-rich extract from Polygonatum sibiricum (PREPS) on hematopoiesis in the mice bearing triple negative breast cancer (TNBC). We found that the 4T1 TNBC tumor significantly increased myeloid cells in peripheral blood, bone marrow and spleen, while decreasing bone marrow hematopoietic stem and progenitor cells (HSPCs), indicative of an inhibition of medullary hematopoiesis. When 4T1 TNBC tumor-bearing mice were treated with PREPS, the percentage of myeloid cells within tumor-infiltrating immune cells was reduced. In addition, PREPS also inhibited hematopoietic cell expansion in the spleen, which was induced by TNBC tumors. Importantly, PREPS markedly increased HSPCs and common lymphoid progenitors in the bone marrow that had been suppressed by TNBC tumors. These findings suggest that PREPS protect hematopoiesis inhibited by TNBC tumors in the bone marrow. Although PREPS alone did not achieve statistical significance in the suppression of TNBC tumor growth, it may have a long-lasting anti-tumor effect to assist TNBC therapies by sustaining hematopoiesis and lymphoid regeneration in bone marrow. [Display omitted] • Triple negative 4T1 tumor increases myelocytes in blood, spleen and bone marrow. • Hematopoietic progenitors decrease in 4T1 mice bone marrow but increase in spleen. • Polysaccharide-rich extract from PS reduces myelocytes in tumor infiltrating cells. • PREPS protects hematopoietic stem and progenitor cells in the bone marrow of 4T1 mice. [ABSTRACT FROM AUTHOR]