|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 July 2001, Vol. 98, No. 2, pp. 495-497
BRIEF REPORT
Expression of p15ink4b gene during
megakaryocytic differentiation of normal and myelodysplastic
hematopoietic progenitors
Luciana Teofili,
Maurizio Martini,
Antonella Di Mario,
Sergio Rutella,
Raffaella Urbano,
Myriam Luongo,
Giuseppe Leone, and
Luigi Maria Larocca
From the Institutes of Hematology and Pathology,
Università Cattolica del Sacro Cuore, Rome, Italy.
In myelodysplastic syndrome (MDS), the expression of the
cyclin-dependent kinase inhibitor p15ink4B (p15) is
frequently decreased because of the aberrant methylation of the gene
promoter; p15 is normally up-regulated during megakaryocytic differentiation. It was hypothesized that p15 methylation and deregulation of gene expression contribute to defective
megakaryocytopoiesis in patients with MDS. Here it is shown that the
increasing autocrine production of TGF- 1 stimulates
megakaryocytic differentiation in normal CD34+ cells and
that p15 mediates, at least in part, this effect. This TGF-1-dependent pathway is altered in MDS CD34+
progenitors because of p15 methylation. The demethylating agent 2-deoxyAZAcytidin can restore the normal demethylated state of the
p15 gene and increase its expression. Nevertheless, MDS
CD34+ cells only poorly differentiate to the megakaryocytic
lineage. These findings suggest that p15 methylation occurs in a
neoplastic clone with a profound defect of cell proliferation,
survival, and differentiation that cannot be overcome by using a
demethylating drug.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Gilles, R. Guieze, D. Bluteau, V. Cordette-Lagarde, C. Lacout, R. Favier, F. Larbret, N. Debili, W. Vainchenker, and H. Raslova
P19INK4D links endomitotic arrest and megakaryocyte maturation and is regulated by AML-1
Blood,
April 15, 2008;
111(8):
4081 - 4091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Muntean, L. Pang, M. Poncz, S. F. Dowdy, G. A. Blobel, and J. D. Crispino
Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization
Blood,
June 15, 2007;
109(12):
5199 - 5207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Kalinina, A. Agrotis, Y. Antropova, O. Ilyinskaya, V. Smirnov, E. Tararak, and A. Bobik
Smad Expression in Human Atherosclerotic Lesions: Evidence for Impaired TGF-{beta}/Smad Signaling in Smooth Muscle Cells of Fibrofatty Lesions
Arterioscler Thromb Vasc Biol,
August 1, 2004;
24(8):
1391 - 1396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Frohling, R. F. Schlenk, J. Breitruck, A. Benner, S. Kreitmeier, K. Tobis, H. Dohner, and K. Dohner
Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm
Blood,
December 15, 2002;
100(13):
4372 - 4380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
