Up-regulation of amphotrophic retroviral receptor expression in human peripheral blood CD34+ cells.

Abstract:

:Retroviral-mediated gene transfer into hematopoietic stem cells provides the only means of stable transduction of these cells and their progeny for use with a variety of potentially therapeutic genes. Expression of the Moloney amphotropic retroviral receptor-pit-2 or GLVR-2-is critical to the recognition and entry of Moloney leukemia virus-derived viruses into human target cells such as CD34+ hematopoietic cells. GLVR-2 functions as a sodium-dependent phosphate transporter as well as a receptor. We have previously shown that the expression of the murine homologue of the amphotropic receptor Ram 1, also a phosphate transporter, is developmentally regulated in murine hematopoietic fetal liver cells. We also demonstrated that culture of murine fetal liver cells in phosphate-free (PO(4)-free) medium increases levels of receptor mRNA and makes murine fetal liver cells susceptible to Moloney amphotropic viral gene transfer. We now examine the effect of culture conditions on the expression of GLVR-2 in human CD34+ cells. In this report, we demonstrate that there is a 2-3 fold increase in GLVR-2 mRNA levels in CD34+ cells after 3 days in culture with interleukin 3, interleukin 6, and stem-cell factor. In addition, the use of PO(4)-free medium increases expression of GLVR-2 an additional 2-fold in these cells during this time. These results indicate that GLVR-2 expression can be up-regulated on these cells, and may permit improved retroviral gene transfer efficiencies.

journal_name

Am J Hematol

authors

Kaubisch A,Ward M,Schoetz S,Hesdorffer C,Bank A

doi

10.1002/(sici)1096-8652(199908)61:4<243::aid-ajh4>

keywords:

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

243-53

issue

4

eissn

0361-8609

issn

1096-8652

pii

10.1002/(SICI)1096-8652(199908)61:4<243::AID-AJH4>

journal_volume

61

pub_type

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