|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3555-3561
Hemoglobin switching in unicellular erythroid culture of sibling
erythroid burst-forming units: kit ligand induces a dose-dependent
fetal hemoglobin reactivation potentiated by sodium butyrate
Marco Gabbianelli,
Ugo Testa,
Adriana Massa,
Elvira Pelosi,
Nadia Maria Sposi,
Roberta Riccioni,
Luisella Luchetti, and
Cesare Peschle
From the Department of Hematology and Oncology, Istituto Superiore
di Sanità, Rome, Italy, and T. Jefferson University, Kimmel
Cancer Center, Philadelphia PA.
Mechanisms underlying fetal hemoglobin (HbF) reactivation in adult
life have not been elucidated; particularly, the role of growth factors
(GFs) is controversial. Interestingly, histone deacetylase (HD)
inhibitors (sodium butyrate, NaB, trichostatin A, TSA) reactivate HbF.
We developed a novel model system to investigate HbF reactivation: (1)
single hematopoietic progenitor cells (HPCs) were seeded in serum-free
unilineage erythroid culture; (2) the 4 daughter cells (erythroid
burst-forming units, [BFU-Es]), endowed with equivalent
proliferation/differentiation and HbF synthesis potential, were seeded
in 4 unicellular erythroid cultures differentially treated with graded
dosages of GFs and/or HD inhibitors; and (3) HbF levels were evaluated
in terminal erythroblasts by assay of F cells and  -globin content
(control levels, 2.4% and 1.8%, respectively, were close to
physiologic values). HbF was moderately enhanced by interleukin-3
(IL-3) and granulocyte-macrophage colony-stimulating factor treatment
(up to 5%-8% -globin content), while sharply reactivated in a
dose-dependent fashion by c-kit ligand (KL) and NaB (20%-23%). The
stimulatory effects of KL on HbF production and erythroid cell
proliferation were strictly correlated. A striking increase of HbF was
induced by combined addition of KL and NaB or TSA (40%-43%). This
positive interaction is seemingly mediated via different mechanisms:
NaB and TSA may modify the chromatin structure of the  -globin gene
cluster; KL may activate the -globin promoter via up-modulation of
tal-1 and possibly FLKF transcription factors. These studies indicate
that KL plays a key role in HbF reactivation in adult life.
Furthermore, combined KL and NaB administration may be considered for
sickle cell anemia and -thalassemia therapy.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
W. Aerbajinai, J. Zhu, C. Kumkhaek, K. Chin, and G. P. Rodgers
SCF induces {gamma}-globin gene expression by regulating downstream transcription factor COUP-TFII
Blood,
July 2, 2009;
114(1):
187 - 194.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Felli, F. Pedini, P. Romania, M. Biffoni, O. Morsilli, G. Castelli, S. Santoro, S. Chicarella, A. Sorrentino, C. Peschle, et al.
MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis
Haematologica,
April 1, 2009;
94(4):
479 - 486.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Qiu, E. N. Olivier, M. Velho, and E. E. Bouhassira
Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells
Blood,
February 15, 2008;
111(4):
2400 - 2408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gabbianelli, O. Morsilli, A. Massa, L. Pasquini, P. Cianciulli, U. Testa, and C. Peschle
Effective erythropoiesis and HbF reactivation induced by kit ligand in -thalassemia
Blood,
January 1, 2008;
111(1):
421 - 429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Felli, L. Fontana, E. Pelosi, R. Botta, D. Bonci, F. Facchiano, F. Liuzzi, V. Lulli, O. Morsilli, S. Santoro, et al.
MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation
PNAS,
December 13, 2005;
102(50):
18081 - 18086.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M Wolk, J E Martin, and R Constantin
Blood cells with fetal haemoglobin (F-cells) detected by immunohistochemistry as indicators of solid tumours
J. Clin. Pathol.,
July 1, 2004;
57(7):
740 - 745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. V. Bhanu, T. A. Trice, Y. T. Lee, and J. L. Miller
A signaling mechanism for growth-related expression of fetal hemoglobin
Blood,
March 1, 2004;
103(5):
1929 - 1933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Zeuner, F. Pedini, M. Signore, U. Testa, E. Pelosi, C. Peschle, and R. De Maria
Stem cell factor protects erythroid precursor cells from chemotherapeutic agents via up-regulation of BCL-2 family proteins
Blood,
July 1, 2003;
102(1):
87 - 93.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gabbianelli, U. Testa, A. Massa, O. Morsilli, E. Saulle, N. M. Sposi, E. Petrucci, G. Mariani, and C. Peschle
HbF reactivation in sibling BFU-E colonies: synergistic interaction of kit ligand with low-dose dexamethasone
Blood,
April 1, 2003;
101(7):
2826 - 2832.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Wojda, K. R. Leigh, J. M. Njoroge, K. A. Jackson, B. Natarajan, M. Stitely, and J. L. Miller
Fetal hemoglobin modulation during human erythropoiesis: stem cell factor has "late" effects related to the expression pattern of CD117
Blood,
January 15, 2003;
101(2):
492 - 497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
