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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1197-1204
HEMATOPOIESIS
HOX-A10 regulates hematopoietic lineage commitment:
evidence for a monocyte-specific transcription factor
Tom Taghon,
Frank Stolz,
Magda De Smedt,
Maggy Cnockaert,
Bruno Verhasselt,
Jean Plum, and
Georges Leclercq
From the Department of Clinical Chemistry, Microbiology
and Immunology, Ghent University, Ghent University Hospital, Ghent,
Belgium; and the Flanders Interuniversity Institute for Biotechnology,
Belgium.
Homeobox genes are well known for their crucial role during
embryogenesis but have also been found to be critically involved in
normal and leukemic hematopoiesis. Because most previous studies focused on the role of aberrant HOX gene expression in
leukemogenesis and because HOX-A10 is expressed in human
CD34+ precursor cells, this study investigated whether
HOX-A10 also plays a pivotal role in normal
hematopoietic-lineage determination. The effect of enforced expression
of this transcription factor on hematopoietic differentiation of highly
purified human cord-blood progenitors was examined by using in vitro
assays. In fetal thymic organ cultures, a dramatic reduction in cells
expressing high levels of HOX-A10 was observed, along with
absence of thymocytes positive for CD3+ T-cell receptor
  . Furthermore, in MS-5 stromal cell cultures, there was a 7-fold
reduction in the number of natural killer cells and a 9-fold reduction
in the number of B cells, thus showing a profound defect in
differentiation toward the lymphoid lineage in
HOX-A10-transduced progenitors. In contrast, the number of CD14+ monocytic cells in the stromal cell culture was
6-fold higher, suggesting an enhanced differentiation toward the
myeloid differentiation pathway of HOX-A10-transduced
progenitors. However, there was a slight reduction in the number of
CD15+ granulocytic cells, which were blocked in their final
maturation. These data show that HOX-A10 can act as an
important key regulator of lineage determination in human hematopoietic
progenitor cells.
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