CELLULAR AND MOLECULAR CHARACTERIZATION OF THE ROLE OF THE FLK-2 FLT-3 RECEPTOR TYROSINE KINASE IN HEMATOPOIETIC STEM-CELLS

The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoiet ic stem cell population and is considered to play a potential role in the developmental fate of the stem cell. Using antibodies derived agai nst the extracellular domain of the receptor, we show that stem cells from both murine fetal liver and bone marrow can express flk-2/flt-3. However, in both these tissues, there are stem cell populations that d o not express the receptor. Cell cycle analysis shows that stem cells that do not express the receptor have a greater percentage of the popu lation in G(0) when compared with the flk-2/fit-3-positive population. Development of agonist antibodies to the receptor shows a proliferati ve role for the receptor in stem cell populations. Stimulation with an agonist antibody gives rise to an expansion of both myeloid and lymph oid cells and this effect is enhanced by the addition of kit ligand. T hese studies serve to further illustrate the importance of the flk-2/f lt-3 receptor in the regulation of the hematopoietic stem cell. (C) 19 94 by The American Society of Hematology.