Analysis of megakaryocyte growth and development factor (thrombopoietin) effects on blast cell and megakaryocyte growth in myelodysplasia.
Thrombocytopenia is a frequent feature of myelodysplastic syndromes (MDS) that could be improved by the use of recombinant human megakaryocyte growth and development factor (rHuMGDF). Using short-term liquid cultures and progenitor assays, we have found that rHuMGDF stimulated DNA synthesis and potentiated leukemic cluster growth of bone marrow mononuclear cells in 10/38 MDS cases (26%). Cytogenetically malignant colonies were detectable in rHuMGDF-stimulated cultures (n=3) by fluorescence in situ hybridization. rHuMGDF was able to stimulate CFU-MK formation in 45% of the samples tested. Finally, rHuMGDF-induced blast cell proliferation correlated with elevated expression of c-MPL, previously identified as a bad prognosis factor in MDS.
Fontenay-Roupie
M
M
Laboratoire d'Hématologie et INSERM U363 ICGM, Université Paris V, Hôpital Cochin, France.
Dupont
J M
JM
Picard
F
F
Fichelson
S
S
Botella
A
A
Melle
J
J
Guesnu
M
M
Casadevall
N
N
Dreyfus
F
F
Bouscary
D
D
D001752:Blast Crisis / Q000473:pathology*; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002999:Clone Cells / Q000166:cytology; D003114:Colony-Forming Units Assay; D004247:DNA / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008533:Megakaryocytes / Q000166:cytology*; D008747:Methylcellulose; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000473:pathology*; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012313:RNA / Q000032:analysis; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000235:genetics; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013926:Thrombopoietin / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human; D012313:RNA; D008747:Methylcellulose; D004247:DNA; D013926:Thrombopoietin