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

Rita Shaknovich, Patricia L. Yeyati, Sarah Ivins, Ari Melnick, Cheryl Lempert, Samuel Waxman, Arthur Z Zelent, Jonathan D. Licht

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)5533-5545
Number of pages13
JournalMolecular and Cellular Biology
Volume18
Issue number9
StatePublished - 1998
Externally publishedYes

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Zinc Fingers
Myeloid Cells
Cell Differentiation
Leukemia
Apoptosis
Growth
Proteins
Acute Promyelocytic Leukemia
Granulocyte-Macrophage Colony-Stimulating Factor
Granulocytes
Cell Cycle
Cell Death

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Shaknovich, R., Yeyati, P. L., Ivins, S., Melnick, A., Lempert, C., Waxman, S., ... Licht, J. D. (1998). The promyelocytic leukemia zinc finger protein affects myeloid cell growth, differentiation, and apoptosis. Molecular and Cellular Biology, 18(9), 5533-5545.

The promyelocytic leukemia zinc finger protein affects myeloid cell growth, differentiation, and apoptosis. / Shaknovich, Rita; Yeyati, Patricia L.; Ivins, Sarah; Melnick, Ari; Lempert, Cheryl; Waxman, Samuel; Zelent, Arthur Z; Licht, Jonathan D.

In: Molecular and Cellular Biology, Vol. 18, No. 9, 1998, p. 5533-5545.

Research output: Contribution to journalArticle

Shaknovich, R, Yeyati, PL, Ivins, S, Melnick, A, Lempert, C, Waxman, S, Zelent, AZ & Licht, JD 1998, 'The promyelocytic leukemia zinc finger protein affects myeloid cell growth, differentiation, and apoptosis', Molecular and Cellular Biology, vol. 18, no. 9, pp. 5533-5545.
Shaknovich R, Yeyati PL, Ivins S, Melnick A, Lempert C, Waxman S et al. The promyelocytic leukemia zinc finger protein affects myeloid cell growth, differentiation, and apoptosis. Molecular and Cellular Biology. 1998;18(9):5533-5545.
Shaknovich, Rita ; Yeyati, Patricia L. ; Ivins, Sarah ; Melnick, Ari ; Lempert, Cheryl ; Waxman, Samuel ; Zelent, Arthur Z ; Licht, Jonathan D. / The promyelocytic leukemia zinc finger protein affects myeloid cell growth, differentiation, and apoptosis. In: Molecular and Cellular Biology. 1998 ; Vol. 18, No. 9. pp. 5533-5545.
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