|
|
 Previous Article | Table of Contents | Next Article 
FLK-2/FLT-3 ligand regulates the growth of early myeloid progenitors
isolated from human fetal liver
MO Muench, MG Roncarolo, S Menon, Y Xu, R Kastelein, S Zurawski, CH Hannum, J Culpepper, F Lee and R Namikawa
Human Immunology and Molecular Biology Departments, DNAX Research
Institute, Palo Alto, CA.
The effects of the recently identified FLK-2/FLT-3 ligand (FL) on the
growth of purified human fetal liver progenitors were investigated under
serum-deprived culture conditions. FL alone was found to stimulate modest
proliferation in short-term cultures of CD34++ CD38+ lineage (Lin)-
light-density fetal liver (LDFL) cells and the more primitive CD34++ CD38-
Lin- LDFL cells. However, the low levels of growth induced by FL were
insufficient for colony formation in clonal cultures. Synergism between FL
and either granulocyte-macrophage colony- stimulating factor (GM-CSF),
interleukin-3 (IL-3) or KIT ligand (KL) was observed in promoting the
growth of high-proliferative potential (HPP) colony-forming cells (CF)
and/or low-proliferative potential (LPP)-CFC in cultures of CD34++ CD38+
Lin- and CD34++ CD38- Lin- LDFL- cells. FL, alone or in combination with
other cytokines, was not found to affect the growth of CD34+ Lin- LDFL
cells, the most mature subpopulation of fetal liver progenitors
investigated. The growth of the most primitive subset of progenitors
studied, CD34++ CD38- Lin- LDFL cells, required the interactions of at
least two cytokines, because only very low levels of growth were observed
in response to either FL, GM-CSF, IL-3 or KL alone. However, the results of
delayed cytokine-addition experiments suggested that individually these
cytokines did promote the survival of this early population of progenitors.
Although two-factor combinations of FL, KL, and GM-CSF were observed to
promote the growth of early progenitors in a synergistic manner, neither of
these factors was found to make fetal liver progenitors more responsive to
suboptimal concentrations of a second cytokine. Only myeloid cells were
recovered from liquid cultures of CD34++ CD38- Lin- LDFL cells grown in the
presence of combinations of FL, KL, and GM-CSF. These results indicate that
FL is part of a network of growth factors that regulate the growth and
survival of early hematopoietic progenitors.
Volume 85,
Issue 4,
pp. 963-972,
02/15/1995
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:
|
|
|
|
 
T. Kimura, R. Asada, J. Wang, T. Kimura, M. Morioka, K. Matsui, K. Kobayashi, K. Henmi, S. Imai, M. Kita, et al.
Identification of Long-Term Repopulating Potential of Human Cord Blood-Derived CD34-flt3- Severe Combined Immunodeficiency-Repopulating Cells by Intra-Bone Marrow Injection
Stem Cells,
June 1, 2007;
25(6):
1348 - 1355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Rocnik, R. Okabe, J.-C. Yu, B. H. Lee, N. Giese, D. P. Schenkein, and D. G. Gilliland
Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD
Blood,
August 15, 2006;
108(4):
1339 - 1345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Grundler, C. Miething, C. Thiede, C. Peschel, and J. Duyster
FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model
Blood,
June 15, 2005;
105(12):
4792 - 4799.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Grundler, C. Thiede, C. Miething, C. Steudel, C. Peschel, and J. Duyster
Sensitivity toward tyrosine kinase inhibitors varies between different activating mutations of the FLT3 receptor
Blood,
July 15, 2003;
102(2):
646 - 651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Sohal, V. T. Phan, P. V. Chan, E. M. Davis, B. Patel, L. M. Kelly, T. J. Abrams, A. M. O'Farrell, D. G. Gilliland, M. M. Le Beau, et al.
A model of APL with FLT3 mutation is responsive to retinoic acid and a receptor tyrosine kinase inhibitor, SU11657
Blood,
April 15, 2003;
101(8):
3188 - 3197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Kelly, Q. Liu, J. L. Kutok, I. R. Williams, C. L. Boulton, and D. G. Gilliland
FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model
Blood,
January 1, 2002;
99(1):
310 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. O. Muench and A. Barcena
Broad Distribution of Colony-Forming Cells with Erythroid, Myeloid, Dendritic Cell, and NK Cell Potential Among CD34++ Fetal Liver Cells
J. Immunol.,
November 1, 2001;
167(9):
4902 - 4909.
[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]
|
|
|
|
|
|
|
R. G. Wickremasinghe and A. V. Hoffbrand
Biochemical and Genetic Control of Apoptosis: Relevance to Normal Hematopoiesis and Hematological Malignancies
Blood,
June 1, 1999;
93(11):
3587 - 3600.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Goff, D. S. Shields, and J. S. Greenberger
Influence of Cytokines on the Growth Kinetics and Immunophenotype of Daughter Cells Resulting From the First Division of Single CD34+Thy-1+lin- Cells
Blood,
December 1, 1998;
92(11):
4098 - 4107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Matsunaga, T. Kato, H. Miyazaki, and M. Ogawa
Thrombopoietin Promotes the Survival of Murine Hematopoietic Long-Term Reconstituting Cells: Comparison With the Effects of FLT3/FLK-2 Ligand and Interleukin-6
Blood,
July 15, 1998;
92(2):
452 - 461.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
M. A. Dao, A. J. Shah, G. M. Crooks, and J. A. Nolta
Engraftment and Retroviral Marking of CD34+ and CD34+CD38- Human Hematopoietic Progenitors Assessed in Immune-Deficient Mice
Blood,
February 15, 1998;
91(4):
1243 - 1255.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Fortunel, P Batard, A Hatzfeld, M. Monier, B Panterne, J Lebkowski, and J Hatzfeld
High proliferative potential-quiescent cells: a working model to study primitive quiescent hematopoietic cells
J. Cell Sci.,
January 7, 1998;
111(13):
1867 - 1875.
[Abstract]
[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]
|
|
|
|
|
|
|
L. Humeau, C. Chabannon, M. T. Firpo, P. Mannoni, C. Bagnis, M.-G. Roncarolo, and R. Namikawa
Successful Reconstitution of Human Hematopoiesis in the SCID-hu Mouse by Genetically Modified, Highly Enriched Progenitors Isolated From Fetal Liver
Blood,
November 1, 1997;
90(9):
3496 - 3506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. J. Borge, V. Ramsfjell, L. Cui, and S. E.W. Jacobsen
Ability of Early Acting Cytokines to Directly Promote Survival and Suppress Apoptosis of Human Primitive CD34+CD38- Bone Marrow Cells With Multilineage Potential at the Single-Cell Level: Key Role of Thrombopoietin
Blood,
September 15, 1997;
90(6):
2282 - 2292.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Strobl, C. Bello-Fernandez, E. Riedl, W. F. Pickl, O. Majdic, S. D. Lyman, and W. Knapp
flt3 Ligand in Cooperation With Transforming Growth Factor-beta 1 Potentiates In Vitro Development of Langerhans-Type Dendritic Cells and Allows Single-Cell Dendritic Cell Cluster Formation Under Serum-Free Conditions
Blood,
August 15, 1997;
90(4):
1425 - 1434.
[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]
|
|
|
|
|
|
|
M. Engelhardt, R. Kumar, J. Albanell, R. Pettengell, W. Han, and M. A.S. Moore
Telomerase Regulation, Cell Cycle, and Telomere Stability in Primitive Hematopoietic Cells
Blood,
July 1, 1997;
90(1):
182 - 193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yonemura, H. Ku, S. D. Lyman, and M. Ogawa
In Vitro Expansion of Hematopoietic Progenitors and Maintenance of Stem Cells: Comparison Between FLT3/FLK-2 Ligand and KIT Ligand
Blood,
March 15, 1997;
89(6):
1915 - 1921.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. O. Muench, M. G. Roncarolo, and R. Namikawa
Phenotypic and Functional Evidence for the Expression of CD4 by Hematopoietic Stem Cells Isolated From Human Fetal Liver
Blood,
February 15, 1997;
89(4):
1364 - 1375.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Beslu, J. LaRose, N. Casteran, D. Birnbaum, E. Lecocq, P. Dubreuil, and R. Rottapel
Phosphatidylinositol-3' Kinase Is Not Required for Mitogenesis or Internalization of the Flt3/Flk2 Receptor Tyrosine Kinase
J. Biol. Chem.,
August 16, 1996;
271(33):
20075 - 20081.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Namikawa, M. Muench, and M. Roncarolo
Regulatory roles of the ligand for Flk2/Flt3 tyrosine kinase receptor on human hematopoiesis
Stem Cells,
July 1, 1996;
14(4):
388 - 395.
[Abstract]
|
|
|
|
|
|
|
M N Lioubin, P A Algate, S Tsai, K Carlberg, A Aebersold, and L R Rohrschneider
p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity.
Genes & Dev.,
May 1, 1996;
10(9):
1084 - 1095.
[Abstract]
[PDF]
|
|
|
|
|
