INCREASED RECRUITMENT OF HEMATOPOIETIC PROGENITOR CELLS UNDERLIES THEEX-VIVO EXPANSION POTENTIAL OF FLT3 LIGAND

The ligand for flt-3 (FLT3L) exhibits striking structural homology wit h stem cell factor (SCF) and monocyte colony-stimulating factor (M-CSF ) and also acts in synergy with a range of other hematopoietic growth factors (HGF). In this study, we show that FLT3L responsive hematopoie tic progenitor cells (HPC) are CD34(+)CD38(-), rhodamine 123(dull), an d hydroperoxycyclophosphamide (4-HC) resistant. To investigate the bas is for the capacity of FLT3L to augment the de novo generation of myel oid progenitors from CD34(+)CD38(-) cells, single bone marrow CD34(+)C D38(-) cells were sorted into Terasaki wells containing serum-free med ium supplemented with interleukin-3 (IL-3), IL-6, granulocyte colony-s timulating factor (G-CSF), SCF (4 HGF) +/- FLT3L. Under these conditio ns, FLT3L recruited approximately twofold more CD34(+)CD38(-) cells in to division than 4 HGF alone. The enhanced proliferative response to F LT3L was evident by day 3 and was maintained at all subsequent time po ints examined. In accord with these findings, we also show that transd uction of CD34(+)CD38(-) cells with the LAPSN retrovirus is enhanced b y FLT3L. The results of these experiments therefore indicate that incr eased recruitment of primitive HPC into cell cycle underlies the ex vi vo expansion potential of FLT3L and also its ability to improve retrov iral transduction of HPC. (C) 1997 by The American Society of Hematolo gy.