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Effect of Direct Cell-to-Cell Interaction between the KM-102 Clonal Human Marrow Stromal Cell Line and the HL-60 Myeloid Leukemic Cell Line on the Differentiation and Proliferation of the HL-60 Line¹

Department of Pathology, Keio University School of Medicine, Shinjiku-ku, Tokyo 160, Japan

Hematopoietic cellular interaction was investigated in a coculture of the human clonal marrow stromal line, KM-102, and the myeloid leukemia cell line, HL-60. In the coculture, a large number of HL-60 cells remained in the supernatant but some of them became firmly attached to KM-102 cells. The attached HL-60 cells showed little positive reaction in the NBT test when the culture was supplemented with 10^-9 to 10^-7 M 1,25-dihydroxyvitamin D₃. In contrast, differentiation in the supernatant HL-60 cells was strikingly responsive to the agent in a dose-dependent way. Furthermore, the complete inhibition was observed in the incorporation of [³H]thymidine into the attached HL-60 cells with autoradiography, but 23.6% of the supernatant cells moderately incorporated [³H] thymidine into their nuclei. There was no attachment between HL-60 cells and stromal cells from human thymus and lymph node, or between lymphocytic leukemia cells and marrow stromal cells. These results indicate that there is direct cellular interaction between myeloid leukemic cells and marrow stromal cells which modulates the proliferation and differentiation of the myeloid leukemic cells. This modulation by marrow stromal cells is more strongly affected by this interaction than by exogenously added differentiation-inducing agents. Apparently marrow stromal cells produce a definitive milieu for the proliferation and differentiation of myeloid leukemic cells.

¹ This work was supported by Grants-in-Aid for Scientific Research and Cancer Research 59480153, 59015090, and 61015094 from the Ministry of Education, Science, and Culture of Japan.

² To whom requests for reprints should be addressed, at the Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjiku-ku, Tokyo 160, Japan.

Received 6/17/86. Revised 2/ 4/87. Accepted 2/25/87.

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