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Cell Growth and Development

The Promyelocytic Leukemia Zinc Finger Protein Affects Myeloid Cell Growth, Differentiation, and Apoptosis

, , , , , , & show all
Pages 5533-5545 | Received 20 Oct 1997, Accepted 26 May 1998, Published online: 28 Mar 2023
 

ABSTRACT

The promyelocytic leukemia zinc finger (PLZF) gene, which is disrupted in therapy-resistant, t(11;17)(q23;q21)-associated acute promyelocytic leukemia (APL), is expressed in immature hematopoietic cells and is down-regulated during differentiation. To determine the role of PLZF in myeloid development, we engineered expression of PLZF in murine 32Dcl3 cells. Expression of PLZF had a dramatic growth-suppressive effect accompanied by accumulation of cells in the G0/G1 compartment of the cell cycle and an increased incidence of apoptosis. PLZF-expressing pools also secreted a growth-inhibitory factor, which could explain the severe growth suppression of PLZF-expressing pools that occurred despite the fact that only half of the cells expressed high levels of PLZF. PLZF overexpression inhibited myeloid differentiation of 32Dcl3 cells in response to granulocyte and granulocyte-macrophage colony-stimulating factors. Furthermore, cells that expressed PLZF appeared immature as demonstrated by morphology, increased expression of Sca-1, and decreased expression of Gr-1. These findings suggest that PLZF is an important regulator of cell growth, death, and differentiation. Disruption of PLZF function associated with t(11;17) may be a critical event leading to APL.

ACKNOWLEDGMENTS

We thank Alan Rosmarin, David Sassoon, and Heidi Stuhlmann for helpful discussions and Steven Arkin and Christine Arkin for assistance with FACS analysis.

This work was supported by NIH grants CA59936 (J.D.L., S.W., and A.Z.), CA73762 (A.M.), American Cancer Society grant DHP-160 (J.D.L.), and the Leukemia Research Fund of Great Britain (A.Z.). J.D.L. is a Scholar of the Leukemia Society of America. R.S.S. was supported by Medical Scientist Training Program grant GM0707280-17 from the NIH. P.L.Y. was supported by the Lauri Strauss Leukemia Fund.

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