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Specific Binding of [³H]Phorbol Dibutyrate to Phorbol Diesterresponsive and -resistant Clones of a Human Myeloid Leukemia (KG-1) Line 1

Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California 90024

Phorbol diesters induce macrophage-like differentiation in KG-1 and HL-60 human acute myelogenous leukemia cell lines. We developed a cloned subline of KG-1, known as KG-1a, that does not differentiate when exposed to phorbol diesters. Both KG-1 and KG-1a cells have a single class of specific high-affinity receptors for labeled phorbol-12,13-dibutyrate with a mean K_d of 1.47 ± 0.10 (S.E.) x 10^-8 M and 0.85 ± 0.20 x 10^-8 M for the sensitive parental KG-1 line and the resistant KG-1a subline, respectively (p < 0.025). The number of [³H]phorbol-12,13-dibutyrate binding sites (mean ± S.E.) per cell was 3.85 ± 0.98 x 10⁵ and 3.94 ± 0.31 x 10⁵ on KG-1 and resistant KG-1a cells, respectively. We observed no significant decrease of specific binding with time (down regulation) in either KG-1, KG-1a, or HL-60 cells, suggesting that down regulation of specific phorbol-12,13-dibutyrate binding is not critical to induction of differentiation. Our data also confirm that the presence of specific highaffinity phorbol receptors on leukemic cells does not assure that phorbol diesters can trigger their differentiation.

¹ Recipient of grants from the NIH (CA 30526) and the USPHS. To whom requests for reprints should be addressed, at Division of Hematology/Oncology, Department of Medicine, 37-068 CHS, Los Angeles, Calif. 90024.

² Recipient of support from the NIH (Grants CA 26038 and CA 32737); the Leukemia Society of America, Inc.; the Bruce Fowler, Jr., Memorial Fund; and the Jonsson Comprehensive Cancer Center. Scholar of the Leukemia Society of America.

Received 9/29/82. Accepted 5/ 3/83.

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