|
|
 Previous Article | Table of Contents | Next Article 
Effect of flt3 ligand on the ex vivo expansion of human CD34+ hematopoietic
progenitor cells
HJ McKenna, P de Vries, K Brasel, SD Lyman and DE Williams
Immunex Corp, Seattle, WA 98101, USA.
A ligand for the tyrosine kinase receptor flt3/flk-2, referred to here as
flt3 ligand (flt3L), was recently cloned. The effect of flt3L on purified
human CD34+ progenitor cells was examined. flt3 receptor (flt3R) was
detected on the surface of human bone marrow cells that were enriched for
CD34 expression. The effects of flt3L and the c-kit ligand Steel factor
(SLF) on hematopoietic progenitors were compared in clonal colony assays.
Both factors synergized with Pixy321 (interleukin- 3
[IL-3]-granulocyte-macrophage colony-stimulating factor fusion protein) to
induce granulocytic-monocytic (GM) and high proliferative potential (HPP)
colonies and synergized with Pixy321 + erythropoietin (EPO) to induce
multipotent granulocytic-erythroid-monocytic- megakaryocytic colonies.
Although SLF had a potent effect on colony formation of erythroid
restricted progenitor cells (burst-forming unit- erythroid), no effect by
flt3L was observed. The addition of flt3L to irradiated long-term marrow
cultures seeded with CD34+ cells augmented both total and progenitor cell
production. Ex vivo expansion studies with isolated CD34+ bone marrow cells
from normal donors showed that flt3L alone supported maintenance of both GM
and HPP progenitors for 3 to 4 weeks in vitro. The addition of flt3L to a
growth factor combination of IL-1 alpha + IL-3 + IL-6 + EPO resulted in a
synergistic effect on progenitor cell expansion comparable to that observed
with the addition of SLF to IL-1 alpha + IL-3 + IL-6 + EPO. These data show
a function for flt3L in the regulation of both primitive multipotent and
lineage-committed hematopoietic progenitor cells.
Volume 86,
Issue 9,
pp. 3413-3420,
11/01/1995
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:
|
|
|
|
 
F. Orlandi, F. M. Venanzi, A. Concetti, H. Yamauchi, S. Tiwari, L. Norton, J. D. Wolchok, A. N. Houghton, and P. D. Gregor
Antibody and CD8+ T Cell Responses against HER2/neu Required for Tumor Eradication after DNA Immunization with a Flt-3 Ligand Fusion Vaccine
Clin. Cancer Res.,
October 15, 2007;
13(20):
6195 - 6203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. B. Aiello, J. R. Keller, K. D. Klarmann, G. Dranoff, R. Mazzucchelli, and S. K. Durum
IL-7 Induces Myelopoiesis and Erythropoiesis
J. Immunol.,
February 1, 2007;
178(3):
1553 - 1563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Ebert, M. M. Lee, J. L. Pretz, A. Subramanian, R. Mak, T. R. Golub, and C. A. Sieff
An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray
Blood,
June 15, 2005;
105(12):
4620 - 4626.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Higano, N. J. Vogelzang, J. A. Sosman, A. Feng, D. Caron, and E. J Small
Safety and Biological Activity of Repeated Doses of Recombinant Human Flt3 Ligand in Patients with Bone Scan-Negative Hormone-Refractory Prostate Cancer
Clin. Cancer Res.,
February 15, 2004;
10(4):
1219 - 1225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Gilliland and J. D. Griffin
The roles of FLT3 in hematopoiesis and leukemia
Blood,
August 13, 2002;
100(5):
1532 - 1542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhang, S. Fukuda, Y. Lee, G. Hangoc, S. Cooper, R. Spolski, W. J. Leonard, and H. E. Broxmeyer
Essential Role of Signal Transducer and Activator of Transcription (Stat)5a but Not Stat5b for Flt3-Dependent Signaling
J. Exp. Med.,
September 5, 2000;
192(5):
719 - 728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Solanilla, J. Dechanet, A. El Andaloussi, M. Dupouy, F. Godard, J. Chabrol, P. Charbord, J. Reiffers, A. T. Nurden, B. Weksler, et al.
CD40-ligand stimulates myelopoiesis by regulating flt3-ligand and thrombopoietin production in bone marrow stromal cells
Blood,
June 15, 2000;
95(12):
3758 - 3764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. McKenna, K. L. Stocking, R. E. Miller, K. Brasel, T. De Smedt, E. Maraskovsky, C. R. Maliszewski, D. H. Lynch, J. Smith, B. Pulendran, et al.
Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells
Blood,
June 1, 2000;
95(11):
3489 - 3497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-C. Shih, M. C.-T. Hu, J. Hu, Y. Weng, P. J. Yazaki, J. Medeiros, and S. J. Forman
A secreted and LIF-mediated stromal cell-derived activity that promotes ex vivo expansion of human hematopoietic stem cells
Blood,
March 15, 2000;
95(6):
1957 - 1966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-F. Arrighi, C. Hauser, B. Chapuis, R. H. Zubler, and V. Kindler
Long-Term Culture of Human CD34+ Progenitors With FLT3-Ligand, Thrombopoietin, and Stem Cell Factor Induces Extensive Amplification of a CD34-CD14- and a CD34-CD14+ Dendritic Cell Precursor
Blood,
April 1, 1999;
93(7):
2244 - 2252.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.A. Dao, K. Hashino, I. Kato, and J.A. Nolta
Adhesion to Fibronectin Maintains Regenerative Capacity During Ex Vivo Culture and Transduction of Human Hematopoietic Stem and Progenitor Cells
Blood,
December 15, 1998;
92(12):
4612 - 4621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-M. Peron, C. Esche, V. M. Subbotin, C. Maliszewski, M. T. Lotze, and M. R. Shurin
FLT3-Ligand Administration Inhibits Liver Metastases: Role of NK Cells
J. Immunol.,
December 1, 1998;
161(11):
6164 - 6170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Kapp, M. Bhatia, D. Bonnet, B. Murdoch, and J. E. Dick
Treatment of Non-Obese Diabetic (NOD)/Severe-Combined Immunodeficient Mice (SCID) With flt3 Ligand and Interleukin-7 Impairs the B-Lineage Commitment of Repopulating Cells After Transplantation of Human Hematopoietic Cells
Blood,
September 15, 1998;
92(6):
2024 - 2031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller, V. McCullar, and C. M. Verfaillie
Ex Vivo Culture of CD34+/Lin-/DR- Cells in Stroma-Derived Soluble Factors, Interleukin-3, and Macrophage Inflammatory Protein-1alpha Maintains Not Only Myeloid But Also Lymphoid Progenitors in a Novel Switch Culture Assay
Blood,
June 15, 1998;
91(12):
4516 - 4522.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Williams, G. G. Pipia, N. S. Datta, and M. W. Long
Thrombopoietin Requires Additional Megakaryocyte-Active Cytokines for Optimal Ex Vivo Expansion of Megakaryocyte Precursor Cells
Blood,
June 1, 1998;
91(11):
4118 - 4126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Shimizu, M. Ogawa, M. Kobayashi, G. Almeida-Porada, and E. D. Zanjani
Engraftment of Cultured Human Hematopoietic Cells in Sheep
Blood,
May 15, 1998;
91(10):
3688 - 3692.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Gotze, M. Ramirez, K. Tabor, D. Small, W. Matthews, and C. I. Civin
Flt3high and Flt3low CD34+ Progenitor Cells Isolated From Human Bone Marrow Are Functionally Distinct
Blood,
March 15, 1998;
91(6):
1947 - 1958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Gaffney, J. Lund, and J. S. Miller
FLT-3 Ligand and Marrow Stroma-Derived Factors Promote CD3gamma , CD3delta , CD3zeta , and RAG-2 Gene Expression in Primary Human CD34+LIN-DR- Marrow Progenitors
Blood,
March 1, 1998;
91(5):
1662 - 1670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Lyman and S. E. W. Jacobsen
c-kit Ligand and Flt3 Ligand: Stem/Progenitor Cell Factors With Overlapping Yet Distinct Activities
Blood,
February 15, 1998;
91(4):
1101 - 1134.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Luens, M. A. Travis, B. P. Chen, B. L. Hill, R. Scollay, and L. J. Murray
Thrombopoietin, kit Ligand, and flk2/flt3 Ligand Together Induce Increased Numbers of Primitive Hematopoietic Progenitors From Human CD34+Thy-1+Lin- Cells With Preserved Ability to Engraft SCID-hu Bone
Blood,
February 15, 1998;
91(4):
1206 - 1215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ebihara, K. Tsuji, S. D. Lyman, X. Sui, M. Yoshida, K. Muraoka, K. Yamada, R. Tanaka, and T. Nakahata
Synergistic Action of Flt3 and gp130 Signalings in Human Hematopoiesis
Blood,
December 1, 1997;
90(11):
4363 - 4368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Dooley, M. Xiao, B. K. Oppenlander, J. M. Plunkett, and S. D. Lyman
Flt3 Ligand Enhances the Yield of Primitive Cells After Ex Vivo Cultivation of CD34+ CD38dim Cells and CD34+ CD38dim CD33dim HLA-DR+ Cells
Blood,
November 15, 1997;
90(10):
3903 - 3913.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. N. Haylock, M. J. Horsfall, T. L. Dowse, H. S. Ramshaw, S. Niutta, S. Protopsaltis, L. Peng, C. Burrell, I. Rappold, H.-J. Buhring, et al.
Increased Recruitment of Hematopoietic Progenitor Cells Underlies the Ex Vivo Expansion Potential of FLT3 Ligand
Blood,
September 15, 1997;
90(6):
2260 - 2272.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Papayannopoulou, B. Nakamoto, R. G. Andrews, S. D. Lyman, and M. Y. Lee
In Vivo Effects of Flt3/Flk2 Ligand on Mobilization of Hematopoietic Progenitors in Primates and Potent Synergistic Enhancement With Granulocyte Colony-Stimulating Factor
Blood,
July 15, 1997;
90(2):
620 - 629.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Piacibello, F. Sanavio, L. Garetto, A. Severino, D. Bergandi, J. Ferrario, F. Fagioli, M. Berger, and M. Aglietta
Extensive Amplification and Self-Renewal of Human Primitive Hematopoietic Stem Cells From Cord Blood
Blood,
April 15, 1997;
89(8):
2644 - 2653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Dao, C. H. Hannum, D. B. Kohn, and J. A. Nolta
FLT3 Ligand Preserves the Ability of Human CD34+ Progenitors to Sustain Long-Term Hematopoiesis in Immune-Deficient Mice After Ex Vivo Retroviral-Mediated Transduction
Blood,
January 15, 1997;
89(2):
446 - 456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
