FLT3/FLK-2 (STK-1) ligand does not stimulate human megakaryopoiesis in vitro

Abstract

It has not yet been determined if the FLT3/FLK-2 or STK-1 Ligand (STK-1 L)FLT3/FLK-2 or STK-1 receptor (STK-1R) axis has the ability to regulate human megakaryopoiesis in vitro. To address this question, we exposed normal human CD34+ marrow mononuclear cells to recombinant human STK-11, alone, or in combination with other growth factors. Colony-forming unit- megakaryocytic/thrombocytes (CFU-Meg) and BEU-E-derived colonies wee then enumerated, and effects on colony size and maturation noted. As assessed by these parameters, STK-11, had no demonstrable effect on megakaryocyte colony formation. Similarly, suppressing STK-1R expression with oligodeoxynucleotides also had no influence on CFU-Meg-derived colony formation. To begin to derive a physiologic explanation for these findings, we examined freshly isolated normal human megakaryocytes for the presence of STK-11, and STK-1R mRNA. In contrast to a growing number of growth factors and growth factor receptors which appear to be expressed by megakaryocytes, normal mature human megakaryocytes express neither STK-1R or STK-1L, mRNA. Accordingly, our results led us to hypothesize that if STK-1/STK-1L, have any effects on megakaryocyte development in vitro, they are likely subtle and of uncertain physiologic significance.