|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 November 2000, Vol. 96, No. 9, pp. 3154-3160
NEOPLASIA
Mutations of the AML1 gene in
myelodysplastic syndrome and their functional implications in
leukemogenesis
Yoichi Imai,
Mineo Kurokawa,
Koji Izutsu,
Akira Hangaishi,
Kengo Takeuchi,
Kazuhiro Maki,
Seishi Ogawa,
Shigeru Chiba,
Kinuko Mitani, and
Hisamaru Hirai
From the Department of Hematology and Oncology and the
Department of Pathology, Graduate School of Medicine, University of
Tokyo, Tokyo, Japan.
The AML1 gene encodes a DNA-binding protein that
contains the runt domain and is the most frequent target of
translocations associated with human leukemias. Here, point mutations
of the AML1 gene, V105ter (single-letter amino acid
code) and R139G, (single-letter amino acid codes)
were identified in 2 cases of myelodysplastic syndrome (MDS) by means
of the reverse transcriptase-polymerase chain reaction single-strand
conformation polymorphism method. Both mutations are present in the
region encoding the runt domain of AML1 and cause
loss of the DNA-binding ability of the resultant products. Of these
mutants, V105ter has also lost the ability to heterodimerize with
polyomavirus enhancer binding protein 2/core binding factor  (PEBP2/CBF). On the other hand, the R139G mutant acts as a
dominant negative inhibitor by competing with wild-type AML1 for
interaction with PEBP2/CBF. This study is the first report that
describes mutations of AML1 in patients with MDS
and the mechanism whereby the mutant acts as a dominant negative
inhibitor of wild-type AML1.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. Watanabe-Okochi, J. Kitaura, R. Ono, H. Harada, Y. Harada, Y. Komeno, H. Nakajima, T. Nosaka, T. Inaba, and T. Kitamura
AML1 mutations induced MDS and MDS/AML in a mouse BMT model
Blood,
April 15, 2008;
111(8):
4297 - 4308.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ichikawa, S. Goyama, T. Asai, M. Kawazu, M. Nakagawa, M. Takeshita, S. Chiba, S. Ogawa, and M. Kurokawa
AML1/Runx1 Negatively Regulates Quiescent Hematopoietic Stem Cells in Adult Hematopoiesis
J. Immunol.,
April 1, 2008;
180(7):
4402 - 4408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Li, K. K. Sinha, M. A. Hay, C. R. Rinaldi, Y. Saunthararajah, and G. Nucifora
RUNX1-RUNX1 Homodimerization Modulates RUNX1 Activity and Function
J. Biol. Chem.,
May 4, 2007;
282(18):
13542 - 13551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cammenga, B. Niebuhr, S. Horn, U. Bergholz, G. Putz, F. Buchholz, J. Lohler, and C. Stocking
RUNX1 DNA-Binding Mutants, Associated with Minimally Differentiated Acute Myelogenous Leukemia, Disrupt Myeloid Differentiation
Cancer Res.,
January 15, 2007;
67(2):
537 - 545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nakagawa, M. Ichikawa, K. Kumano, S. Goyama, M. Kawazu, T. Asai, S. Ogawa, M. Kurokawa, and S. Chiba
AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis
Blood,
November 15, 2006;
108(10):
3329 - 3334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Hamelin, C. Letourneux, P.-H. Romeo, F. Porteu, and M. Gaudry
Thrombopoietin regulates IEX-1 gene expression through ERK-induced AML1 phosphorylation
Blood,
April 15, 2006;
107(8):
3106 - 3113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Heller, A. C. Glembotsky, M. J. Gandhi, C. L. Cummings, C. J. Pirola, R. F. Marta, L. I. Kornblihtt, J. G. Drachman, and F. C. Molinas
Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutation
Blood,
June 15, 2005;
105(12):
4664 - 4670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Fukushima-Nakase, Y. Naoe, I. Taniuchi, H. Hosoi, T. Sugimoto, and T. Okuda
Shared and distinct roles mediated through C-terminal subdomains of acute myeloid leukemia/Runt-related transcription factor molecules in murine development
Blood,
June 1, 2005;
105(11):
4298 - 4307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Nguyen, P. P. Pandolfi, Y. Aikawa, Y. Tagata, M. Ohki, and I. Kitabayashi
Physical and functional link of the leukemia-associated factors AML1 and PML
Blood,
January 1, 2005;
105(1):
292 - 300.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Goyama, Y. Yamaguchi, Y. Imai, M. Kawazu, M. Nakagawa, T. Asai, K. Kumano, K. Mitani, S. Ogawa, S. Chiba, et al.
The transcriptionally active form of AML1 is required for hematopoietic rescue of the AML1-deficient embryonic para-aortic splanchnopleural (P-Sp) region
Blood,
December 1, 2004;
104(12):
3558 - 3564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Sun and J. R. Downing
Haploinsufficiency of AML1 results in a decrease in the number of LTR-HSCs while simultaneously inducing an increase in more mature progenitors
Blood,
December 1, 2004;
104(12):
3565 - 3572.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. H. Christiansen, M. K. Andersen, and J. Pedersen-Bjergaard
Mutations of AML1 are common in therapy-related myelodysplasia following therapy with alkylating agents and are significantly associated with deletion or loss of chromosome arm 7q and with subsequent leukemic transformation
Blood,
September 1, 2004;
104(5):
1474 - 1481.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Harada, Y. Harada, H. Niimi, T. Kyo, A. Kimura, and T. Inaba
High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia
Blood,
March 15, 2004;
103(6):
2316 - 2324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Imai, M. Kurokawa, Y. Yamaguchi, K. Izutsu, E. Nitta, K. Mitani, M. Satake, T. Noda, Y. Ito, and H. Hirai
The Corepressor mSin3A Regulates Phosphorylation-Induced Activation, Intranuclear Location, and Stability of AML1
Mol. Cell. Biol.,
February 1, 2004;
24(3):
1033 - 1043.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nishimura, Y. Fukushima-Nakase, Y. Fujita, M. Nakao, S. Toda, N. Kitamura, T. Abe, and T. Okuda
VWRPY motif-dependent and -independent roles of AML1/Runx1 transcription factor in murine hematopoietic development
Blood,
January 15, 2004;
103(2):
562 - 570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Li, J. Yan, C. J. Matheny, T. Corpora, J. Bravo, A. J. Warren, J. H. Bushweller, and N. A. Speck
Energetic Contribution of Residues in the Runx1 Runt Domain to DNA Binding
J. Biol. Chem.,
August 29, 2003;
278(35):
33088 - 33096.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hirai
Molecular Mechanisms of Myelodysplastic Syndrome
Jpn. J. Clin. Oncol.,
April 1, 2003;
33(4):
153 - 160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Kalev-Zylinska, J. A. Horsfield, M. V. C. Flores, J. H. Postlethwait, M. R. Vitas, A. M. Baas, P. S. Crosier, and K. E. Crosier
Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis
Development,
March 6, 2003;
129(8):
2015 - 2030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Harada, Y. Harada, H. Tanaka, A. Kimura, and T. Inaba
Implications of somatic mutations in the AML1 gene in radiation-associated and therapy-related myelodysplastic syndrome/acute myeloid leukemia
Blood,
January 15, 2003;
101(2):
673 - 680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Leroy, C. Roumier, N. Grardel-Duflos, E. Macintyre, P. Lepelley, P. Fenaux, and C. Preudhomme
Unlike AML1, CBFbeta gene is not deregulated by point mutations in acute myeloid leukemia and in myelodysplastic syndromes
Blood,
May 15, 2002;
99(10):
3848 - 3850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Michaud, F. Wu, M. Osato, G. M. Cottles, M. Yanagida, N. Asou, K. Shigesada, Y. Ito, K. F. Benson, W. H. Raskind, et al.
In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis
Blood,
February 15, 2002;
99(4):
1364 - 1372.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Buijs, P. Poddighe, R. van Wijk, W. van Solinge, E. Borst, L. Verdonck, A. Hagenbeek, P. Pearson, and H. Lokhorst
A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies
Blood,
November 1, 2001;
98(9):
2856 - 2858.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
