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EVI1 is expressed in megakaryocyte cell lineage and enforced expression of EVI1 in UT-7/GM cells induces megakaryocyte differentiation.

Abstract：

:3q21q26 syndrome, an acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with chromosomal translocations or inversions between the bands 3q21 and 3q26, is frequently associated with dysmegakaryocytopoiesis and increased platelet counts at the initial diagnosis. Since the EVI1 gene at 3q26 is transcriptionally activated in 3q21q26 syndrome, we assessed the role of EVI1 gene expression in the abnormal megakaryocytic differentiation in 3q21q26 syndrome. RT-PCR analysis of various types of hematopoietic cells revealed that the EVI1 gene is expressed specifically in CD34(+) cells, megakaryocytes, and platelets. UT-7 is a human immature megakaryoblastic leukemia cell line with dependence for the growth on granulocyte-macrophage colony-stimulating factor (GM-CSF) (designated at UT-7/GM) and with a differentiation capacity to erythroid (UT-7/EPO) and megakaryocytic lineages (UT-7/TPO) by erythropoietin (EPO) and thrombopoietin (TPO), respectively. Among three UT-7 sublines, UT-7/GM, UT-7/EPO, and UT-7/TPO, expression of the EVI1 gene was detected at low levels in UT-7/GM and UT-7/EPO cells, but was detected at a higher level in UT-7/TPO cells. When UT-7/GM cells were cultured with TPO, the level of EVI1 expression was increased, along with increased numbers of polynuclear megakaryocytes and expression of the platelet factor 4 (PF-4) gene. Furthermore, forced expression of the EVI1 gene in UT-7/GM cells changed their morphology to polynuclear megakaryocytes, stopped their growth, and induced cell death within a month. These data indicate that expression of the EVI1 gene is involved in progression of megakaryocytic differentiation and, thus, the dysmegakaryocytopoiesis in 3q21q26 syndrome could be partly due to an enhanced differentiation capacity of leukemia cells and/or megakaryocytes by constitutive expression of the EVI1 gene.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Shimizu S,Nagasawa T,Katoh O,Komatsu N,Yokota J,Morishita K

doi

10.1006/bbrc.2002.6693

subject

Has Abstract

pub_date

2002-04-05 00:00:00

pages

609-16

issue

eissn

0006-291X

issn

1090-2104

pii

S0006291X02966933

journal_volume

292

pub_type

杂志文章

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EVI1 is expressed in megakaryocyte cell lineage and enforced expression of EVI1 in UT-7/GM cells induces megakaryocyte differentiation.