|
|
 Previous Article | Table of Contents | Next Article 
Retroviral-mediated gene expression in human myelomonocytic cells: a
comparison of hematopoietic cell promoters to viral promoters
P Malik, WJ Krall, XJ Yu, C Zhou and DB Kohn
Division of Research Immunology/Bone Marrow Transplantation, Childrens
Hospital, Los Angeles, University of Southern California School of
Medicine, USA.
Gene transfer into human hematopoietic stem cells with expression targeted
to the maturing myelomonocytic progeny has applications for gene therapy of
genetic diseases affecting granulocytes and macrophages. We hypothesized
that promoters of myeloid-specific genes that are upregulated with
myelomonocytic differentiation would also upregulate expression of an
exogenous gene in a retroviral vector. Moloney murine leukemia virus
(MoMuLV)-based retroviral vectors using promoters from hematopoietic genes
(CD11b, CD18, and CD34) were compared with vectors with viral promoters
(MoMuLV long terminal repeat [LTR], cytomegalovirus [CMV], and simian virus
40 [SV40]). Human glucocerebrosidase (GC) cDNA was the reporter gene. HL60
cells were transduced with these vectors and vector-derived GC activity was
compared in undifferentiated HL-60 cells and the same cells differentiated
into granulocytes using dimethyl sulfoxide or monocyte/macrophages using
phorbol myristate acetate. In undifferentiated HL-60 cells, vector-derived
GC activity was the highest when it was controlled by the MoMuLV LTR. In
HL-60 cells differentiated into granulocytes, vector-derived GC activity
transcribed from the CD11b, MoMuLV LTR, and CMV promoters was equivalent to
1.7, 1.5, and 1.5 times the normal endogenous GC activity, respectively,
and 0.8, 2.0, and 3.6 times the normal GC activity, respectively, in those
differentiated into macrophages. With granulocytic differentiation, the
CD11b promoter showed maximal induction in GC activity (8-fold); with
macrophage differentiation, the CD11b promoter showed a fourfold induction
in GC expression. The CD11b promoter also generated significant levels of
GC activity in the myelomonocytic progeny of transduced CD34+ cells.
Expression from the CD11b promoter, unlike that from the CMV or the MoMuLV
LTR promoters, was relatively myelomonocyte-specific, with minimal
expression observed in Jurkat T cells or HeLa carcinoma cells. The
induction of expression from the CD11b promoter with differentiation in
HL-60 cells correlates with the developmental regulation of the CD11b gene.
Retroviral vectors using the CD11b promoter have potential utility for gene
therapy of disorders affecting the myelomonocytic lineage.
Volume 86,
Issue 8,
pp. 2993-3005,
10/15/1995
Copyright © 1995 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. L. Farmen, P. H. Karp, P. Ng, D. J. Palmer, D. R. Koehler, J. Hu, A. L. Beaudet, J. Zabner, and M. J. Welsh
Gene transfer of CFTR to airway epithelia: low levels of expression are sufficient to correct Cl- transport and overexpression can generate basolateral CFTR
Am J Physiol Lung Cell Mol Physiol,
December 1, 2005;
289(6):
L1123 - L1130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Toh, S. Kawashima, M. Kawai, T. Sakoda, T. Ueyama, S. Satomi-Kobayashi, S. Hirayama, and M. Yokoyama
Transplantation of cardiotrophin-1-expressing myoblasts to the left ventricular wall alleviates the transition from compensatory hypertrophy to congestive heart failure in Dahl salt-sensitive hypertensive rats
J. Am. Coll. Cardiol.,
June 16, 2004;
43(12):
2337 - 2347.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Freeman, M. S. Roberts, C. A. Vogler, A. Nicholes, A. A. Hofling, and M. S. Sands
Behavior and Therapeutic Efficacy of beta -Glucuronidase-Positive Mononuclear Phagocytes in a Murine Model of Mucopolysaccharidosis Type VII
Blood,
September 15, 1999;
94(6):
2142 - 2150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Worgall, R. Singh, P. L. Leopold, R. J. Kaner, N. R. Hackett, N. Topf, M. A.S. Moore, and R. G. Crystal
Selective Expansion of Alveolar Macrophages In Vivo by Adenovirus-Mediated Transfer of the Murine Granulocyte-Macrophage Colony-Stimulating Factor cDNA
Blood,
January 15, 1999;
93(2):
655 - 666.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Malik, T. C. Fisher, L. L.W. Barsky, L. Zeng, P. Izadi, A. L. Hiti, K. I. Weinberg, T. D. Coates, H. J. Meiselman, and D. B. Kohn
An In Vitro Model of Human Red Blood Cell Production From Hematopoietic Progenitor Cells
Blood,
April 15, 1998;
91(8):
2664 - 2671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Tenen, R. Hromas, J. D. Licht, and D.-E. Zhang
Transcription Factors, Normal Myeloid Development, and Leukemia
Blood,
July 15, 1997;
90(2):
489 - 519.
[Full Text]
[PDF]
|
|
|
|
|
