FLT3/FLK-2 (STK-1) Ligand does not stimulate human megakaryopoiesis in vitro.
It has not yet been determined if the FLT3/FLK-2 or STK-1 Ligand (STK-1L)/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-1L alone, or in combination with other growth factors. Colony-forming unit-megakaryocytic/thrombocytes (CFU-Meg) and BFU-E-derived colonies were then enumerated, and effects on colony size and maturation noted. As assessed by these parameters, STK-1L 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-1L 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.
Ratajczak
M Z
MZ
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Ratajczak
J
J
Ford
J
J
Kregenow
R
R
Marlicz
W
W
Gewirtz
A M
AM
D018952:Antigens, CD34 / Q000032:analysis; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008533:Megakaryocytes / Q000737:chemistry / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D051941:fms-Like Tyrosine Kinase 3
D018952:Antigens, CD34; D003115:Colony-Stimulating Factors; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C084881:flt3 ligand protein; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3