Human bone marrow heparan sulfate induces leukemia cell differentiation

The proliferation and development of hematopoietic cells occurs in close association with bone marrow stroma. Heparan sulfate is a major component of the stroma. We have isolated a form of heparan sulfate proteoglycan from a human stromal cell line grown in vitro in the presence of [35S]sulfate. This proteoglycan contains a phosphatidylinositol component which likely anchors it to the stromal cell membrane. The glycosaminoglycan chains of this proteoglycan could induce maturation of the HL-60 myeloid leukemia cell line. A less hydrophobic heparan sulfate proteoglycan was also present in the stroma, but could not induce HL-60 maturation. The two heparan sulfates had glycosaminoglycan chains that were similar in size (36 Kd) and charge density. Structural studies suggested only minor but perhaps significant differences in the carbohydrate sequences of the two heparan sulfates. The relationship of these subtle structural differences to the difference observed in differentiation-inducing activity remains to be elucidated.