Implication of a new molecule IK in CD34+ hematopoietic progenitor cell
proliferation and differentiation
LX Cao, MC Le Bousse-Kerdiles, D Clay, S Oshevski, C Jasmin and P Krief
Division of Hematology, State University of New York, Stony Brook, USA.
HLA-DR is one of the markers associated with hematopoietic cell
differentiation, since expression of this molecule is modulated throughout
hematopoiesis. We have previously described and cloned the gene encoding
factor IK, which inhibits both interferon gamma (IFN- gamma)-induced and
constitutive HLA-DR expression. The current study demonstrates that IK gene
transcripts are present in CD34+ cells purified from human umbilical cord
blood. IK expression increased and was therefore inversely correlated with
the gradual loss of HLA-DR during growth factor-induced CD34+ cell
proliferation and differentiation. To study the possible role of IK in
hematopoiesis, antisense probes were used. IK expression was specifically
inhibited by an antisense oligodeoxynucleotide containing two
phosphorothioate internucleotide linkages at each of the 3' and 5' ends and
corresponding to the initiation site of IK mRNA. A control oligonucleotide
was also tested in parallel. A specific decrease of IK transcripts was
correlated with an increase of HLA-DR antigen expression level. In
colony-forming assays, IK antisense oligonucleotide inhibited colony
formation by multilineage early erythroid and granulomonocytic CD34+
progenitors. The mean colony size was decreased 70% by IK antisense
oligonucleotide in comparison to controls. These results provide evidence
that the IK molecule participates in the regulation of HLA-DR expression on
hematopoietic cells and plays a role in growth factor-dependent CD34+ cell
proliferation and differentiation by modulating HLA-DR expression.
Volume 89,
Issue 10,
pp. 3615-3623,
05/15/1997
Copyright © 1997 by The American Society of Hematology
