RT Journal Article
SR Electronic
T1 EVI1 and MDS1/EVI1 Expression During Primary Human Hematopoietic Progenitor Cell Differentiation into Various Myeloid Lineages
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4883
OP 4889
VO 32
IS 11
A1 KATARINA STEINLEITNER
A1 PAULINA RAMPETSREITER
A1 RENE KÖFFEL
A1 GAJALAKSHMI RAMANATHAN
A1 CHRISTINE MANNHALTER
A1 HERBERT STROBL
A1 ROTRAUD WIESER
YR 2012
UL http://ar.iiarjournals.org/content/32/11/4883.abstract
AB Background and Aim: Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in myeloid leukemia. We therefore studied its expression and function in cluster of differentiation 34-positive (CD34+) primary human hematopoietic progenitor cells. Materials and Methods: CD34+ cells were differentiated into various myeloid lineages using the appropriate cytokines. EVI1 expression was measured by quantitative real time reverse transcriptase-polymerase chain reaction (qRT-PCR) and intranuclear fluorescence-activated cell sorting (FACS). Experimental manipulation of EVI1 levels was achieved using retroviral infection. Results: EVI1 mRNA and its variant myelodysplastic syndrome 1 (MDS1)/EVI1, which gives rise to a partially antagonistic protein, were detectable in CD34+ cells, but their levels declined rapidly during differentiation into the granulocyte, monocyte, dendritic, erythroid, and megakaryocyte lineages. Similarly, EVI1 protein levels decreased during myeloid differentiation. Attempts to experimentally express EVI1 in CD34+ and U937 cells indicated that ectopic expression of EVI1 may cause growth arrest, apoptosis and/or senescence of human hematopoietic cells. Conclusion: EVI1 is expressed in human hematopoietic progenitor cells, but is down-regulated during differentiation. Ectopic expression of EVI1 may activate cellular safeguards against oncogene activation.