IMPLICATION OF A NEW MOLECULE IK IN CD34(-CELL PROLIFERATION AND DIFFERENTIATION() HEMATOPOIETIC PROGENITOR)

HLA-DR is one of the markets associated with hematopoietic cell differ entiation, since expression of this molecule is mod ulated throughout hematopoiesis. We have previously described and cloned the gene encodi ng factor IK, which inhibits both interferon gamma (IFN-gamma)-induced and constitutive HLA-DR expression, The current study demonstrates th at IK gene transcripts are present in CD34(+) cells purified from huma n umbilical cord blood, IK expression increased and was therefore inve rsely correlated with the gradual loss of HLA-DR during growth factor- induced CD34(+) cell proliferation and differentiation. To study the p ossible role of IK in hematopoiesis, antisense probes were used. IK ex pression was specifically inhibited by an antisense oligodeoxynucleoti de containing two phosphorothioate internucleotide linkages at each of the 3' and 5' ends and corresponding to the initiation site of IK mRN A. A control oligonucleotide was also tested in parallel. A specific d ecrease of IK transcripts was correlated with an increase of HLA-DR an tigen expression level. In colony-forming assays, IK antisense oligonu cleotide inhibited colony formation by multilineage early erythroid an d granulomonocytic CD34(+) progenitors. The mean colony size was decre ased 70% by IK antisense oligonucleotide in comparison to controls, Th ese results provide evidence that the IK molecule participates in the regulation of HLA-DR expression on hematopoietic cells and plays a rol e in growth factor-dependent CD34(+) cell proliferation and differenti ation by modulating HLA-DR expression. (C) 1997 by The American Societ y of Hematology.