Flt3/Flk-2 ligand in combination with thrombopoietin decreases apoptosis in megakaryocyte development.
The growth factors thrombopoietin (TPO) and Flt3/Flk-2-ligand (FL), either independently or in combination, modulate megakaryocyte development. Our results show that bone marrow CD34+ cells cultured with TPO and FL differentiate at a slower rate into CD41+ cells and are delayed in apoptosis at the later stages of the cultures compared to cells cultured with TPO alone. Our data also show that FL in synergy with TPO may inhibit apoptosis in megakaryocyte development by up-regulating bcl-2 and inducing conformational changes of p53, in MK progenitors. FL in combination with TPO slows down maturation and consequently delays apoptosis of MK progenitor cells.
Sigurjonsson
Olafur Eysteinn
OE
The Blood Bank, Department of Basic Research, Landspitali-University Hospital, 121 Reykjavik, Iceland. olafur.sigurjonsson@labmed.uio.no
Gudmundsson
Kristbjorn Orri
KO
Haraldsdottir
Vilhelmina
V
Rafnar
Thorunn
T
Agnarsson
Bjarni A
BA
Gudmundsson
Sveinn
S
D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects*; D008565:Membrane Proteins / Q000494:pharmacology*; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013926:Thrombopoietin / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D008565:Membrane Proteins; D040201:Platelet Membrane Glycoprotein IIb; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; C084881:flt3 ligand protein; D013926:Thrombopoietin