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The role of the homeobox gene, HOX B7, in human myelomonocytic
differentiation
MC Lill, JF Fuller, R Herzig, GM Crooks and JC Gasson
Department of Medicine and Biological Chemistry, UCLA School of Medicine
90024-1678.
Homeobox genes encode transcription factors known to be important
morphogenic regulators during embryogenesis. An increasing body of work
implies a role for homeobox genes in both hematopoiesis and oncogenesis. We
have analyzed the role of the homeobox gene, HOX B7, in the program of
differentiation of the biphenotypic myeloid cell line, HL60. Induction of
monocytic differentiation in HL-60 cells by vitamin D3 resulted in rapid
expression of HOX B7 mRNA, but stimulation with phorbol ester or dimethyl
sulfoxide (DMSO) did not. Constitutive overexpression of HOX B7 in the HL60
cell line inhibited the granulocytic differentiation associated with
stimulation with DMSO or retinoic acid, but had no effect on the monocytic
differentiation induced by vitamin D3. Normal human monocytes do not
constitutively express HOX B7, nor are they able to be induced to do so by
stimulation with colony-stimulating factor 1 (CSF-1) and gamma interferon
(IFN gamma), or with vitamin D3 and lipopolysaccharide. Human bone marrow
(BM) cells were found to express HOX B7 in response to granulocyte-
macrophage CSF (GM-CSF) and antisense oligonucleotides directed against HOX
B7 inhibited the formation of colonies derived from GM-CSF- stimulated BM.
These data suggest a critical role for HOX B7 in myelomonocytic
differentiation.
Volume 85,
Issue 3,
pp. 692-697,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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