|
|
 Previous Article | Table of Contents | Next Article 
The Partner Gene of AML1 in t(16;21) Myeloid Malignancies Is a
Novel Member of the MTG8(ETO) Family
Toshie Gamou,
Eiko Kitamura,
Fumie Hosoda,
Kimiko Shimizu,
Kenji Shinohara,
Yasuhide Hayashi,
Takahiro Nagase,
Yasunobu Yokoyama, and
Misao Ohki
From the Radiobiology Division, National Cancer Center Research
Institute, Tokyo; Division of Hematology, Department of Medicine,
Yamaguchi Prefecture Central Hospital, Yamaguchi; Department of
Pediatrics, Faculty of Medicine, University of Tokyo, Tokyo; Kazusa DNA
Research Institute, Chiba; and the Center for Molecular Biology and
Cytogenetics, SRL, Inc, Tokyo, Japan.
The t(16;21)(q24;q22) translocation is a rare but recurrent
chromosomal abnormality associated with therapy-related myeloid malignancies and a variant of the t(8;21) translocation in which the
AML1 gene on chromosome 21 is rearranged. Here we report the molecular definition of this chromosomal aberration in four patients. We cloned cDNAs from the leukemic cells of a patient carrying t(16;21)
by the reverse transcription polymerase chain reaction using an
AML1-specific primer. The structural analysis of the cDNAs
showed that AML1 was fused to a novel gene named MTG16
(Myeloid Translocation Gene on chromosome
16) which shows high homology to MTG8
(ETO/CDR) and MTGR1. Northern blot analysis using
MTG16 probes mainly detected 4.5 kb and 4.2 kb RNAs, along with
several other minor RNAs in various human tissues. As in t(8;21), the t(16;21) breakpoints occurred between the exons 5 and 6 of
AML1, and between the exons 1 and 2 or the exons 3 and 4 of
MTG16. The two genes are fused in-frame, resulting in the
characteristic chimeric transcripts of this translocation. Although the
reciprocal chimeric product, MTG16-AML1, was also detected in
one of the t(16;21) patients, its protein product was predicted to be
truncated. Thus, the AML1-MTG16 gene fusion in t(16;21)
leukemia results in the production of a protein that is very similar to
the AML1-MTG8 chimeric protein.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4028-4037
© 1998 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:
|
|
|
|
 
E. DE BRAEKELEER, C. FEREC, and M. DE BRAEKELEER
RUNX1 Translocations in Malignant Hemopathies
Anticancer Res,
April 1, 2009;
29(4):
1031 - 1037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Chyla, I. Moreno-Miralles, M. A. Steapleton, M. A. Thompson, S. Bhaskara, M. Engel, and S. W. Hiebert
Deletion of Mtg16, a Target of t(16;21), Alters Hematopoietic Progenitor Cell Proliferation and Lineage Allocation
Mol. Cell. Biol.,
October 15, 2008;
28(20):
6234 - 6247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Hamlett, J. Draper, J. Strouboulis, F. Iborra, C. Porcher, and P. Vyas
Characterization of megakaryocyte GATA1-interacting proteins: the corepressor ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation
Blood,
October 1, 2008;
112(7):
2738 - 2749.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kumar, K. M. Cheney, R. McKirdy, P. M. Neilsen, R. B. Schulz, J. Lee, J. Cohen, G. W. Booker, and D. F. Callen
CBFA2T3-ZNF652 Corepressor Complex Regulates Transcription of the E-box Gene HEB
J. Biol. Chem.,
July 4, 2008;
283(27):
19026 - 19038.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. F. Peterson, M. Yan, and D.-E. Zhang
The p21Waf1 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein AML1-ETO
Blood,
May 15, 2007;
109(10):
4392 - 4398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kumar, J. Manning, H. E. Spendlove, G. Kremmidiotis, R. McKirdy, J. Lee, D. N. Millband, K. M. Cheney, M. R. Stampfer, P. P. Dwivedi, et al.
ZNF652, A Novel Zinc Finger Protein, Interacts with the Putative Breast Tumor Suppressor CBFA2T3 to Repress Transcription
Mol. Cancer Res.,
September 1, 2006;
4(9):
655 - 665.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Brown, C. R. Wilkinson, S. R. Waterman, C. H. Kok, D. G. Salerno, S. M. Diakiw, B. Reynolds, H. S. Scott, A. Tsykin, G. F. Glonek, et al.
Genetic regulators of myelopoiesis and leukemic signaling identified by gene profiling and linear modeling
J. Leukoc. Biol.,
August 1, 2006;
80(2):
433 - 447.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Schuh, A. J. Tipping, A. J. Clark, I. Hamlett, B. Guyot, F. J. Iborra, P. Rodriguez, J. Strouboulis, T. Enver, P. Vyas, et al.
ETO-2 Associates with SCL in Erythroid Cells and Megakaryocytes and Provides Repressor Functions in Erythropoiesis
Mol. Cell. Biol.,
December 1, 2005;
25(23):
10235 - 10250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Amann, B. J. I. Chyla, T. C. Ellis, A. Martinez, A. C. Moore, J. L. Franklin, L. McGhee, S. Meyers, J. E. Ohm, K. S. Luce, et al.
Mtgr1 Is a Transcriptional Corepressor That Is Required for Maintenance of the Secretory Cell Lineage in the Small Intestine
Mol. Cell. Biol.,
November 1, 2005;
25(21):
9576 - 9585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ishizuka and M. A. Lazar
The Nuclear Receptor Corepressor Deacetylase Activating Domain Is Essential for Repression by Thyroid Hormone Receptor
Mol. Endocrinol.,
June 1, 2005;
19(6):
1443 - 1451.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Giresi, E. J. Stevenson, J. Theilhaber, A. Koncarevic, J. Parkington, R. A. Fielding, and S. C. Kandarian
Identification of a molecular signature of sarcopenia
Physiol Genomics,
April 14, 2005;
21(2):
253 - 263.
[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]
|
|
|
|
|
|
|
V. Ibanez, A. Sharma, S. Buonamici, A. Verma, S. Kalakonda, J. Wang, S. Kadkol, and Y. Saunthararajah
AML1-ETO Decreases ETO-2 (MTG16) Interactions with Nuclear Receptor Corepressor, an Effect That Impairs Granulocyte Differentiation
Cancer Res.,
July 1, 2004;
64(13):
4547 - 4554.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-Y. Cho, Y. Akbarali, L. F. Zerbini, X. Gu, J. Boltax, Y. Wang, P. Oettgen, D.-E. Zhang, and T. A. Libermann
Isoforms of the Ets Transcription Factor NERF/ELF-2 Physically Interact with AML1 and Mediate Opposing Effects on AML1-mediated Transcription of the B Cell-specific blk Gene
J. Biol. Chem.,
May 7, 2004;
279(19):
19512 - 19522.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Chevallier, C. M. Corcoran, C. Lennon, E. Hyjek, A. Chadburn, V. J. Bardwell, J. D. Licht, and A. Melnick
ETO protein of t(8;21) AML is a corepressor for Bcl-6 B-cell lymphoma oncoprotein
Blood,
February 15, 2004;
103(4):
1454 - 1463.
[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]
|
|
|
|
|
|
|
K. Barseguian, B. Lutterbach, S. W. Hiebert, J. Nickerson, J. B. Lian, J. L. Stein, A. J. van Wijnen, and G. S. Stein
Multiple subnuclear targeting signals of the leukemia-related AML1/ETO and ETO repressor proteins
PNAS,
November 26, 2002;
99(24):
15434 - 15439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kochetkova, O. L. D. McKenzie, A. J. Bais, J. M. Martin, G. A. Secker, R. Seshadri, J. A. Powell, S. J. Hinze, A. E. Gardner, H. E. Spendlove, et al.
CBFA2T3 (MTG16) Is a Putative Breast Tumor Suppressor Gene from the Breast Cancer Loss of Heterozygosity Region at 16q24.3
Cancer Res.,
August 15, 2002;
62(16):
4599 - 4604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang, P. Strissel, R. Strick, J. Chen, G. Nucifora, M. M. Le Beau, R. A. Larson, and J. D. Rowley
Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia
PNAS,
February 20, 2002;
(2002)
42702899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. V. Schillace, S. F. Andrews, G. A. Liberty, M. P. Davey, and D. W. Carr
Identification and Characterization of Myeloid Translocation Gene 16b as a Novel A Kinase Anchoring Protein in T Lymphocytes
J. Immunol.,
February 15, 2002;
168(4):
1590 - 1599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Amann, J. Nip, D. K. Strom, B. Lutterbach, H. Harada, N. Lenny, J. R. Downing, S. Meyers, and S. W. Hiebert
ETO, a Target of t(8;21) in Acute Leukemia, Makes Distinct Contacts with Multiple Histone Deacetylases and Binds mSin3A through Its Oligomerization Domain
Mol. Cell. Biol.,
October 1, 2001;
21(19):
6470 - 6483.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yuan, L. Zhou, T. Miyamoto, H. Iwasaki, N. Harakawa, C. J. Hetherington, S. A. Burel, E. Lagasse, I. L. Weissman, K. Akashi, et al.
AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations
PNAS,
August 28, 2001;
98(18):
10398 - 10403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Burel, N. Harakawa, L. Zhou, T. Pabst, D. G. Tenen, and D.-E. Zhang
Dichotomy of AML1-ETO Functions: Growth Arrest versus Block of Differentiation
Mol. Cell. Biol.,
August 15, 2001;
21(16):
5577 - 5590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Miller, T. Stacy, P. P. Liu, and N. A. Speck
Core-binding factor {beta} (CBF{beta}), but not CBF{beta}-smooth muscle myosin heavy chain, rescues definitive hematopoiesis in CBF{beta}-deficient embryonic stem cells
Blood,
April 15, 2001;
97(8):
2248 - 2256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Hromas, T. Busse, A. Carroll, D. Mack, R. Shopnick, D.-E. Zhang, H. Nakshatri, and K. Richkind
Fusion AML1 transcript in a radiation-associated leukemia results in a truncated inhibitory AML1 protein
Blood,
April 1, 2001;
97(7):
2168 - 2170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zhang, B. A. Hug, E. Y. Huang, C. W. Chen, V. Gelmetti, M. Maccarana, S. Minucci, P. G. Pelicci, and M. A. Lazar
Oligomerization of ETO Is Obligatory for Corepressor Interaction
Mol. Cell. Biol.,
January 1, 2001;
21(1):
156 - 163.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. D. Wood, F. C. Nucifora Jr., K. Duan, C. Zhang, J. Wang, Y. Kim, G. Schilling, N. Sacchi, J. M. Liu, and C. A. Ross
Atrophin-1, the Dentato-Rubral and Pallido-Luysian Atrophy Gene Product, Interacts with Eto/Mtg8 in the Nuclear Matrix and Represses Transcription
J. Cell Biol.,
September 4, 2000;
150(5):
939 - 948.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Shimada, H. Ichikawa, S. Nakamura, R. Katsu, M. Iwasa, I. Kitabayashi, and M. Ohki
Analysis of genes under the downstream control of the t(8;21) fusion protein AML1-MTG8: overexpression of the TIS11b (ERF-1, cMG1) gene induces myeloid cell proliferation in response to G-CSF
Blood,
July 15, 2000;
96(2):
655 - 663.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Okuda, K. Takeda, Y. Fujita, M. Nishimura, S. Yagyu, M. Yoshida, S. Akira, J. R. Downing, and T. Abe
Biological Characteristics of the Leukemia-Associated Transcriptional Factor AML1 Disclosed by Hematopoietic Rescue of AML1-Deficient Embryonic Stem Cells by Using a Knock-in Strategy
Mol. Cell. Biol.,
January 1, 2000;
20(1):
319 - 328.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
B. Lutterbach, Y. Hou, K. L. Durst, and S. W. Hiebert
The inv(16) encodes an acute myeloid leukemia 1 transcriptional corepressor
PNAS,
October 26, 1999;
96(22):
12822 - 12827.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Michelson, M. W. Collard, A. J. Ziemba, J. Persinger, B. Bartholomew, and J. I. Huggenvik
Nuclear DEAF-1-related (NUDR) Protein Contains a Novel DNA Binding Domain and Represses Transcription of the Heterogeneous Nuclear Ribonucleoprotein A2/B1 Promoter
J. Biol. Chem.,
October 22, 1999;
274(43):
30510 - 30519.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fenrick, J. M. Amann, B. Lutterbach, L. Wang, J. J. Westendorf, J. R. Downing, and S. W. Hiebert
Both TEL and AML-1 Contribute Repression Domains to the t(12;21) Fusion Protein
Mol. Cell. Biol.,
October 1, 1999;
19(10):
6566 - 6574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. F. Lewis, T. Stacy, W. R. Green, L. Taddesse-Heath, J. W. Hartley, and N. A. Speck
Core-Binding Factor Influences the Disease Specificity of Moloney Murine Leukemia Virus
J. Virol.,
July 1, 1999;
73(7):
5535 - 5547.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
B. Lutterbach, J. J. Westendorf, B. Linggi, A. Patten, M. Moniwa, J. R. Davie, K. D. Huynh, V. J. Bardwell, R. M. Lavinsky, M. G. Rosenfeld, et al.
ETO, a Target of t(8;21) in Acute Leukemia, Interacts with the N-CoR and mSin3 Corepressors
Mol. Cell. Biol.,
December 1, 1998;
18(12):
7176 - 7184.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. Roulston, R. Espinosa III, G. Nucifora, R. A. Larson, M. M. Le Beau, and J. D. Rowley
CBFA2(AML1) Translocations With Novel Partner Chromosomes in Myeloid Leukemias: Association With Prior Therapy
Blood,
October 15, 1998;
92(8):
2879 - 2885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-Y. Tang, J. Shi, L. Zhang, A. Davis, J. Bravo, A. J. Warren, N. A. Speck, and J. H. Bushweller
Energetic and Functional Contribution of Residues in the Core Binding Factor beta (CBFbeta ) Subunit to Heterodimerization with CBFalpha
J. Biol. Chem.,
December 8, 2000;
275(50):
39579 - 39588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang, P. Strissel, R. Strick, J. Chen, G. Nucifora, M. M. Le Beau, R. A. Larson, and J. D. Rowley
Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia
PNAS,
March 5, 2002;
99(5):
3070 - 3075.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
