HUMAN BONE-MARROW HEPARAN-SULFATE INDUCES LEUKEMIA-CELL DIFFERENTIATION

The proliferation and development of hematopoietic cells occurs in clo se association with bone marrow stroma. Heparan sulfate is a major com ponent of the stroma. We have isolated a form of heparan sulfate prote oglycan from a human stromal cell line grown in vitro in the presence of [S-35]sulfate. This proteoglycan contains a phosphatidylinositol co mponent which likely anchors it to the stromal cell membrane, The glyc osaminoglycan chains of this proteoglycan could induce maturation of t he HL-60 myeloid leukemia cell line. A less hydrophobic heparan sulfat e 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 studi es suggested only minor but perhaps significant differences in the car bohydrate sequences of the two heparan sulfates. The relationship of t hese subtle structural differences to the difference observed in diffe rentiation-inducing activity remains to be elucidated.