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Expression of HOXC4, HOXC5, and HOXC6 in human lymphoid cell lines,
leukemias, and benign and malignant lymphoid tissue
J Bijl, JW van Oostveen, M Kreike, E Rieger, LM van der Raaij-Helmer, JM Walboomers, G Corte, E Boncinelli, AJ van den Brule and CJ Meijer
Department of Pathology, Free University Hospital, Amsterdam, The
Netherlands.
Besides their regulatory role in embryogenesis, homeobox (HOX) genes are
expressed in a specific manner in hematopoietic cell lineages, implying a
role in the molecular regulation of hematopoiesis. Some HOX C cluster genes
are found to be expressed in lymphoid cells of mice and humans. Their
function and expression in normal hematopoiesis are still largely unknown.
We have studied the mRNA expression of HOXC4, HOXC5, and HOXC6 in several
stages of lymphocyte maturation by reverse transcriptase-polymerase chain
reaction (RT-PCR) and RNA in situ hybridization (RISH). We examined
CD34+/CD38low and CD34+/CD38high cells obtained from normal donor bone
marrow (BM), a panel of 19 lymphoid cell lines, several types of leukemias
and non-Hodgkin's lymphomas (NHL), and lymphocytes isolated from tonsillar
tissue and peripheral blood (PB). HOXC4 and HOXC6 were found to be
expressed during maturation in B- and T-lymphoid cells. The expression of
each gene was found to be initiated at different cell maturation stages.
HOXC4 transcripts were present in CD34+/CD38low cells, which are thought to
comprise stem cells and noncommitted progenitor cells, and in subsequent
stages to terminally maturated lymphoid cells. HOXC6 expression is
initiated in equivalents of prothymocyte and pre-pre-B cell stage and
remains present in mature cells. However, HOXC5 is only expressed in
neoplastic cell lines and in neoplastic cells of NHL, but not in CD34+ BM
cells, nor in resting or activated lymphoid cells isolated from tonsil, PB,
or in leukemia cells. In cell lines, weak expression of HOXC5 is initiated
in equivalents of pre-B cell and common thymocyte stage and is continuously
expressed in mature cell lines. Semi-quantitative RT-PCR showed that
expression levels of HOXC5 were much lower than those of HOXC4 and HOXC6;
furthermore an increase of expression of HOXC4, HOXC5, and HOXC6 during
lymphoid cell differentiation was demonstrated. Thus, mainly mature
lymphoid cell lines and neoplastic cells of NHL do express HOXC5, in
contrast to the lack of expression in normal lymphoid cells and leukemias.
These findings suggest involvement of HOXC5 in lymphomagenesis.
Volume 87,
Issue 5,
pp. 1737-1745,
03/01/1996
Copyright © 1996 by The American Society of Hematology
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