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PMID: 9710637 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The promyelocytic leukemia zinc finger protein affects myeloid cell growth, differentiation, and apoptosis.

Molecular and cellular biology ·Vol. 18 ·No. 9 ·1998-09-00 ·Pages 5533-45

Shaknovich R, Yeyati PL, Ivins S, Melnick A, Lempert C, Waxman S, Zelent A, Licht JD

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.

MeSH Terms
Animals Apoptosis Cell Cycle/physiology Cell Differentiation/drug effects Cell Division/drug effects Cell Line Culture Media, Conditioned DNA-Binding Proteins/biosynthesis,physiology G1 Phase Granulocyte Colony-Stimulating Factor/pharmacology Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology Growth Inhibitors/biosynthesis Hematopoietic Stem Cells/cytology Humans Interleukin-3/pharmacology Kruppel-Like Transcription Factors Mice Promyelocytic Leukemia Zinc Finger Protein Recombinant Proteins/biosynthesis Resting Phase, Cell Cycle Transcription Factors/biosynthesis,physiology Transfection Zinc Fingers
Chemicals
Culture Media, Conditioned DNA-Binding Proteins Growth Inhibitors Interleukin-3 Kruppel-Like Transcription Factors Promyelocytic Leukemia Zinc Finger Protein Recombinant Proteins Transcription Factors Zbtb16 protein, mouse Granulocyte Colony-Stimulating Factor ZBTB16 protein, human Granulocyte-Macrophage Colony-Stimulating Factor
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Shaknovich R
Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, New York, New York, USA.
Yeyati P L
Ivins S
Melnick A
Lempert C
Waxman S
Zelent A
Licht J D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.9.5533
Published
1998-09-00
Pages
5533-45
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC109138
Subset
IM
Grants
NCI NIH HHS · CA59936 · United States
NCI NIH HHS · CA73762 · United States
NIGMS NIH HHS · GM0707280-17 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.9.5533 PMC Full Text View journal details
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