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A diverged homeobox gene is involved in the proliferation and lineage
commitment of human hematopoietic progenitors and highly expressed in acute
myelogenous leukemia
Y Deguchi, A Kirschenbaum and JH Kehrl
Laboratory of Immunoregulation, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
HB24 is a diverged homeobox gene known to be expressed in hematopoietic
progenitor cells. We show here that the inhibition of HB24 expression in
CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the
proliferation of these cells in response to interleukin-3 and
granulocyte-macrophage colony-stimulating factor. The treatment of CD34+
cells with HB24 AS oligonucleotides also reduced the levels of c- fos,
c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells
treated with control oligonucleotides. Conversely, the transient
transfection of HB24 into a subpopulation of CD34 cells inhibited their
differentiation into mature hematopoietic cell types. In addition, HB24
messenger RNA transcripts were elevated in bone marrow and peripheral blood
mononuclear cells isolated from patients with acute myelogenous leukemia
compared with normal controls. These data suggest that HB24 is an important
transcription factor during hematopoietic progenitor proliferation and that
differentiation to specific cell types requires its downregulation.
Furthermore, dysregulated expression of HB24 impairs the normal
differentiation of hematopoietic progenitors and may contribute to
leukemogenesis.
Volume 79,
Issue 11,
pp. 2841-2848,
06/01/1992
Copyright © 1992 by The American Society of Hematology
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