Monocytic differentiation of HL-60 promyelocytic leukemia cells correlates with the induction of Bcl-x(L)

Devasis Chatterjee, Zhiyong Han, John Mendoza, Lee Goodglick, Eric A. Hendrickson, Panayotis Pantazis, James H. Wyche

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34 Scopus citations

Abstract

Treatment of human promyelocytic leukemia HL-60 cells with phorbol esters ultimately induces the differentiation of these cells along the monocyte/macrophage lineage, whereas treatment with retinoic acid or DMSO induces granulocytic/neutrophillic differentiation. In this study, we demonstrate the disparate fates of HL-60 cells treated with the phorbol ester 12,13-phorbol dibutyric acid (PDBu) or DMSO. After DMSO treatment, HL-60 cells eventually died via apoptosis, whereas the viability of PDBu-treated cells was not affected during the same interval. The levels of the apoptosis effector proteins Bak and Bad were enhanced, whereas there was a slight down- regulation of the apoptosis suppressor protein Bcl-2 after treatment of the cells with PDBu and DMSO. Treatment with DMSO resulted in the elevation of the apoptosis effector Bax, whereas treatment with PDBu did not significantly alter the levels of this protein. However, treatment of HL-60 cells with PDBu induced the rapid expression of the apoptosis suppressor protein Bcl-X(L), whereas the expression of this protein remained unaltered in DMSO-treated cells. The generality of this finding was confirmed by the induction of Bcl- X(L) in human myeloid U-937 cells, human peripheral blood monocytes exposed to phorbol ester, and mouse thioglycollate-activated and resident peritoneal macrophages. PDBu-treated HL-60 cells remained viable for 7 days and thereafter began to die via apoptosis, with a concomitant down-regulation of Bcl-x(L). In conclusion, we propose that Bcl-x(L) expression is associated with differentiation and survival of hematopoietic cells along the monocyte/macrophage lineage.

Original languageEnglish (US)
Pages (from-to)1083-1089
Number of pages7
JournalCell Growth and Differentiation
Volume8
Issue number10
StatePublished - Oct 1 1997

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