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Differential expression of a novel proline-rich homeobox gene (Prh) in
human hematolymphopoietic cells
G Manfioletti, V Gattei, E Buratti, A Rustighi, A De Iuliis, D Aldinucci, GH Goodwin and A Pinto
Dipartimento di Biochimica, Biofisica Chimica delle Macromolecole,
Universita di Trieste, Italy.
Proline-rich homeobox (Prh) is a novel human homeobox-containing gene
recently isolated from the CD34+ cell line KG-1A, and whose expression
appears mainly restricted to hematopoietic tissues. To define the pattern
of Prh expression within the human hematopoietic system, we have analyzed
its constitutive expression in purified cells obtained from normal
hematopoietic tissues, its levels of transcription in a number of
leukemia/lymphoma cell lines representing different lineages and stages of
hematolymphopoietic differentiation, and its regulation during in vitro
maturation of human leukemic cell lines. Prh transcripts were not detected
in leukemic cells of T-lymphoid lineage, irrespective of their maturation
stage, and in resting or activated normal T cells from peripheral blood and
lymphoid tissues. In contrast, high levels of Prh expression were shown in
cells representing early stages of B lymphoid maturation, being maintained
up to the level of circulating and tissue mature B cells. Terminal B-cell
differentiation appeared to be conversely associated with the deactivation
of the gene, since preplasmacytic and plasmocytoma cell lines were found
not to express Prh mRNA. Prh transcripts were also shown in human cell
lines of early myelomonocytic, erythromegakaryocytic, and preosteoclast
phenotypes. Prh expression was lost upon in vitro differentiation of
leukemic cell lines into mature monocyte-macrophages and megakaryocytes,
whereas it was maintained or upregulated after induction of maturation to
granulocytes and osteoclasts. Accordingly, circulating normal monocytes did
not display Prh mRNA, which was conversely detected at high levels in
purified normal granulocytes. Our data, which show that the acquisition of
the differentiated phenotype is associated to Prh downregulation in certain
hematopoietic cells but not in others, also suggest that a dysregulated
expression of this gene might contribute to the process of leukemogenesis
within specific cell lineages.
Volume 85,
Issue 5,
pp. 1237-1245,
03/01/1995
Copyright © 1995 by The American Society of Hematology
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