Erythropoiesis in polycythemia vera is hyper-proliferative and has accelerated maturation.
Polycythemia vera (PV) is an acquired myeloproliferative clonal disorder, characterized by augmented erythropoiesis. To better define PV pathogenesis, we performed an in vitro erythroid expansion from peripheral blood mononuclear cells of controls and PV patients and evaluated the cells for proliferation, apoptosis, erythroid differentiation, and morphology at the defined time points. PV erythroid progenitors exhibited increased proliferation at days 9-14 and accelerated maturation at days 7-14, with a larger S-phase population (40%) than controls (20%) at day 11; however, the proportion of apoptotic cells was comparable to controls. Previously, we have identified PV-specific dysregulation of several microRNAs (i.e. miR-150, 451, 222, 155, 378). We had analyzed expression profiles of selected target genes of these microRNAs based on in silico prediction and their known function pertinent to the observed PV-specific erythropoiesis differences. p27, cMYB and EPOR showed differential expression in PV erythroid progenitors at the specific stages of erythroid differentiation. In this study, we identified accelerated maturation and hyper-proliferation at early stages of PV erythropoiesis. We speculate that aberrant expression of p27, c-MYB, and EPOR may contribute to these abnormal features in PV erythropoiesis.
Bruchova
Hana
H
Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
Yoon
Donghoon
D
Agarwal
Archana M
AM
Swierczek
Sabina
S
Prchal
Josef T
JT
D002453:Cell Cycle; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D041905:Erythroid Cells / Q000166:cytology / Q000473:pathology*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000473:pathology; D004920:Erythropoiesis; D005786:Gene Expression Regulation; D020570:Genes, myb / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D011087:Polycythemia Vera / Q000235:genetics* / Q000503:physiopathology*; D017467:Receptors, Erythropoietin / Q000235:genetics
D035683:MicroRNAs; D017467:Receptors, Erythropoietin; D050760:Cyclin-Dependent Kinase Inhibitor p27