Leukemia translocation gene, PLZF, is expressed with a speckled nuclear pattern in early hematopoietic progenitors

Abstract

The PLZF gene was discovered by studying a rearrangement of the RAR alpha locus in a patient with acute promyelocytic leukemia and a t(11;17) chromosomal translocation. To understand further the potential role(s) of the PLZF gene product in hematopoiesis, we have examined its expression levels in a variety of murine tissues and in established cell lines that are representative of various stages of myeloid and lymphoid development. We show that murine PLZF(mPLZF) is expressed at the highest levels in undifferentiated, multipotential hematopoietic progenitor cells and that its expression declines as cells become more mature and committed to various hematopoietic lineages. Data obtained with established cell lines are corroborated by results showing the lack of human PLZF protein expression in mature peripheral blood mononuclear cells and high PLZF levels in the nuclei of CD34+ human bone marrow progenitor cells. Interestingly, unlike many transcription factors, PLZF protein in these cells possesses distinct punctate nuclear distribution, suggesting its compartmentalization in the nucleus. Taken together, our data suggest a role for PLZF protein in early hematopoiesis and the requirement of downregulation of its expression for proper differentiation of most hematopoietic lineages.