|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 August 2002, Vol. 100, No. 3, pp. 998-1007
NEOPLASIA
Heterozygous PU.1 mutations are associated with acute
myeloid leukemia
Beatrice U. Mueller,
Thomas Pabst,
Motomi Osato,
Norio Asou,
Lisa M. Johansen,
Mark D. Minden,
Gerhard Behre,
Wolfgang Hiddemann,
Yoshiaki Ito, and
Daniel G. Tenen
From the Harvard Institutes of Medicine,
Harvard Medical School, Boston, MA; the Department of Internal
Medicine, Kumamoto University, Japan; the Department of Viral Oncology,
Institute for Virus Research, Kyoto University, Kyoto, Japan; the
Department of Medicine and Medical Biophysics, University of Toronto,
Canada; the Department of Medicine III, Grosshadern, Clinical
Cooperative Group Acute Myeloid Leukemia of the National Research
Center for Environment and Health (GSF), Munich, Germany.
The transcription factor PU.1 is required for normal blood cell
development. PU.1 regulates the expression of a number of crucial
myeloid genes, such as the macrophage colony-stimulating factor
(M-CSF) receptor, the granulocyte colony-stimulating factor (G-CSF) receptor, and the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor. Myeloid cells derived from
PU.1 / mice are blocked at the earliest stage of myeloid
differentiation, similar to the blast cells that are the hallmark of
human acute myeloid leukemia (AML). These facts led us to hypothesize
that molecular abnormalities involving the PU.1 gene could
contribute to the development of AML. We identified 10 mutant alleles
of the PU.1 gene in 9 of 126 AML patients. The PU.1 mutations comprised 5 deletions affecting the DNA-binding domain, and 5 point mutations in
1) the DNA-binding domain (2 patients), 2) the PEST domain (2 patients), and 3) the transactivation domain (one patient). DNA binding
to and transactivation of the M-CSF receptor promoter, a direct PU.1
target gene, were deficient in the 7 PU.1 mutants that affected the
DNA-binding domain. In addition, these mutations decreased the ability
of PU.1 to synergize with PU.1-interacting proteins such as AML1 or
c-Jun in the activation of PU.1 target genes. This is the first report
of mutations in the PU.1 gene in human neoplasia and suggests that
disruption of PU.1 function contributes to the block in differentiation
found in AML patients.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Letters in Blood Online:
-
Are PU.1 mutations frequent genetic events in acute myeloid leukemia (AML)?
- Charlotte Lamandin, Christophe Sagot, Christophe Roumier, Pascale Lepelley, Stéphane De Botton, Alain Cosson, Pierre Fenaux, and Claude Preudhomme
Blood 2002 100: 4680.
[Full Text]
[PDF]
-
Heterozygous PU.1 mutations are associated with acute myeloid leukemia
- Beatrice U. Mueller, Thomas Pabst, Motomi Osato, Norio Asou, Lisa M. Johansen, Mark D. Minden, Gerhard Behre, Wolfgang Hiddemann, Yoshiaki Ito, and Daniel G. Tenen
Blood 2003 101: 2074.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
S.-J. Zhang, L.-Y. Ma, Q.-H. Huang, G. Li, B.-W. Gu, X.-D. Gao, J.-Y. Shi, Y.-Y. Wang, L. Gao, X. Cai, et al.
Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia
PNAS,
February 12, 2008;
105(6):
2076 - 2081.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Miranda, R. L. Redner, and D. E. Johnson
Inhibition of Src family kinases enhances retinoic acid induced gene expression and myeloid differentiation
Mol. Cancer Ther.,
December 1, 2007;
6(12):
3081 - 3090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Yeamans, D. Wang, I. Paz-Priel, B. E. Torbett, D. G. Tenen, and A. D. Friedman
C/EBP{alpha} binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment
Blood,
November 1, 2007;
110(9):
3136 - 3142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Papetti and A. I. Skoultchi
Reprogramming Leukemia Cells to Terminal Differentiation and Growth Arrest by RNA Interference of PU.1
Mol. Cancer Res.,
October 1, 2007;
5(10):
1053 - 1062.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Link, G. Kunter, Y. Kasai, Y. Zhao, T. Miner, M. D. McLellan, R. E. Ries, D. Kapur, R. Nagarajan, D. C. Dale, et al.
Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia
Blood,
September 1, 2007;
110(5):
1648 - 1655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tatetsu, S. Ueno, H. Hata, Y. Yamada, M. Takeya, H. Mitsuya, D. G. Tenen, and Y. Okuno
Down-regulation of PU.1 by Methylation of Distal Regulatory Elements and the Promoter Is Required for Myeloma Cell Growth
Cancer Res.,
June 1, 2007;
67(11):
5328 - 5336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Huang, E. Horvath, and E. A. Eklund
PU.1, Interferon Regulatory Factor (IRF) 2, and the Interferon Consensus Sequence-binding Protein (ICSBP/IRF8) Cooperate to Activate NF1 Transcription in Differentiating Myeloid Cells
J. Biol. Chem.,
March 2, 2007;
282(9):
6629 - 6643.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Wlodarski, Q. Zhang, X. Liu, M. Kasprzycka, M. Marzec, and M. A. Wasik
PU.1 Activates Transcription of SHP-1 Gene in Hematopoietic Cells
J. Biol. Chem.,
March 2, 2007;
282(9):
6316 - 6323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Walter, R. E. Ries, J. R. Armstrong, J. S. Park, E. R. Mardis, and T. J. Ley
Expression of a bcr-1 isoform of RAR{alpha}-PML does not affect the penetrance of acute promyelocytic leukemia or the acquisition of an interstitial deletion on mouse chromosome 2
Blood,
February 1, 2007;
109(3):
1237 - 1240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Cook
Is PU.1 pivotal to APL?
Blood,
April 15, 2006;
107(8):
3017 - 3018.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. U. Mueller, T. Pabst, J. Fos, V. Petkovic, M. F. Fey, N. Asou, U. Buergi, and D. G. Tenen
ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression
Blood,
April 15, 2006;
107(8):
3330 - 3338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Metcalf, A. Dakic, S. Mifsud, L. Di Rago, L. Wu, and S. Nutt
Inactivation of PU.1 in adult mice leads to the development of myeloid leukemia
PNAS,
January 31, 2006;
103(5):
1486 - 1491.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Du, S. E. Spence, N. A. Jenkins, and N. G. Copeland
Cooperating cancer-gene identification through oncogenic-retrovirus-induced insertional mutagenesis
Blood,
October 1, 2005;
106(7):
2498 - 2505.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Rosenbauer, S. Koschmieder, U. Steidl, and D. G. Tenen
Effect of transcription-factor concentrations on leukemic stem cells
Blood,
September 1, 2005;
106(5):
1519 - 1524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Iwasaki, C. Somoza, H. Shigematsu, E. A. Duprez, J. Iwasaki-Arai, S.-i. Mizuno, Y. Arinobu, K. Geary, P. Zhang, T. Dayaram, et al.
Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation
Blood,
September 1, 2005;
106(5):
1590 - 1600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Walter, J. S. Park, R. E. Ries, S. K. M. Lau, M. McLellan, S. Jaeger, R. K. Wilson, E. R. Mardis, and T. J. Ley
Reduced PU.1 expression causes myeloid progenitor expansion and increased leukemia penetrance in mice expressing PML-RAR{alpha}
PNAS,
August 30, 2005;
102(35):
12513 - 12518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Yang, W. Khalaf, L. van de Locht, J. H. Jansen, M. Gao, M. A. Thompson, B. A. van der Reijden, D. H. Gutmann, R. Delwel, D. W. Clapp, et al.
Transcriptional Repression of the Neurofibromatosis-1 Tumor Suppressor by the t(8;21) Fusion Protein
Mol. Cell. Biol.,
July 15, 2005;
25(14):
5869 - 5879.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. T. Porse, D. Bryder, K. Theilgaard-Monch, M. S. Hasemann, K. Anderson, I. Damgaard, S. E. W. Jacobsen, and C. Nerlov
Loss of C/EBP{alpha} cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage
J. Exp. Med.,
July 5, 2005;
202(1):
85 - 96.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zhong, A. Takeda, R. Nazari, H. Shio, G. Blobel, and N. R. Yaseen
Carrier-independent Nuclear Import of the Transcription Factor PU.1 via RanGTP-stimulated Binding to Nup153
J. Biol. Chem.,
March 18, 2005;
280(11):
10675 - 10682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Nutt, D. Metcalf, A. D'Amico, M. Polli, and L. Wu
Dynamic regulation of PU.1 expression in multipotent hematopoietic progenitors
J. Exp. Med.,
January 18, 2005;
201(2):
221 - 231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. D. Cook, B. J. McCaw, C. Herring, D. L. John, S. J. Foote, S. L. Nutt, and J. M. Adams
PU.1 is a suppressor of myeloid leukemia, inactivated in mice by gene deletion and mutation of its DNA binding domain
Blood,
December 1, 2004;
104(12):
3437 - 3444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Rosenbauer, K. Wagner, P. Zhang, K.-P. Knobeloch, A. Iwama, and D. G. Tenen
pDP4, a novel glycoprotein secreted by mature granulocytes, is regulated by transcription factor PU.1
Blood,
June 1, 2004;
103(11):
4294 - 4301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Lee, H. Y. Chung, L. A. Ehrlich, D. F. Jelinek, N. S. Callander, G. D. Roodman, and S. J. Choi
IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells
Blood,
March 15, 2004;
103(6):
2308 - 2315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Zheng, A. D. Friedman, M. Levis, L. Li, E. G. Weir, and D. Small
Internal tandem duplication mutation of FLT3 blocks myeloid differentiation through suppression of C/EBP{alpha} expression
Blood,
March 1, 2004;
103(5):
1883 - 1890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Ley, P. J. Minx, M. J. Walter, R. E. Ries, H. Sun, M. McLellan, J. F. DiPersio, D. C. Link, M. H. Tomasson, T. A. Graubert, et al.
A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes
PNAS,
November 25, 2003;
100(24):
14275 - 14280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Dohner, K. Tobis, T. Bischof, S. Hein, R. F. Schlenk, S. Frohling, H. Dohner, B. U. Mueller, T. Pabst, M. Osato, et al.
Mutation analysis of the transcription factor PU.1 in younger adults (16 to 60 years) with acute myeloid leukemia: a study of the AML Study Group Ulm (AMLSG ULM)
Blood,
November 15, 2003;
102(10):
3850 - 3851.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Choe, F. Radparvar, I. Matushansky, N. Rekhtman, X. Han, and A. I. Skoultchi
Reversal of Tumorigenicity and the Block to Differentiation in Erythroleukemia Cells by GATA-1
Cancer Res.,
October 1, 2003;
63(19):
6363 - 6369.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kummalue and A. D. Friedman
Cross-talk between regulators of myeloid development: C/EBP{alpha} binds and activates the promoter of the PU.1 gene
J. Leukoc. Biol.,
September 1, 2003;
74(3):
464 - 470.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. U. Mueller, T. Pabst, M. Osato, N. Asou, L. M. Johansen, M. D. Minden, G. Behre, W. Hiddemann, Y. Ito, and D. G. Tenen
Heterozygous PU.1 mutations are associated with acute myeloid leukemia
Blood,
March 1, 2003;
101(5):
2074 - 2074.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Vangala, M. S. Heiss-Neumann, J. S. Rangatia, S. M. Singh, C. Schoch, D. G. Tenen, W. Hiddemann, and G. Behre
The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia
Blood,
January 1, 2003;
101(1):
270 - 277.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lamandin, C. Sagot, C. Roumier, P. Lepelley, S. De Botton, A. Cosson, P. Fenaux, and C. Preudhomme
Are PU.1 mutations frequent genetic events in acute myeloid leukemia (AML)?
Blood,
December 15, 2002;
100(13):
4680 - 4680.
[Full Text]
[PDF]
|
|
|
| |
