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Science 7 November 1997:
Vol. 278. no. 5340, pp. 1059 - 1064
DOI: 10.1126/science.278.5340.1059
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Articles

Oncogenic Transcription Factors in the Human Acute Leukemias

A. Thomas Look

Chromosomal translocations in the human acute leukemias rearrange the regulatory and coding regions of a variety of transcription factor genes. The resultant protein products can interfere with regulatory cascades that control the growth, differentiation, and survival of normal blood cell precursors. Support for this interpretation comes from the results of gene manipulation studies in mice, as well as the sequence homology of oncogenic transcription factors with proteins known to regulate embryonic development in primitive organisms, including the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Many of these genetic alterations have important prognostic implications that can guide the selection of therapy. The insights gained from studies of translocation-generated oncogenes and their protein products should hasten the development of highly specific, and hence less toxic, forms of leukemia therapy.

The author is at the Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, and the Department of Pediatrics, University of Tennessee College of Medicine, Memphis, TN 38163, USA. E-mail: thomas.look{at}stjude.org

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Translocation Products in Acute Myeloid Leukemia Activate the Wnt Signaling Pathway in Hematopoietic Cells.
C. Muller-Tidow, B. Steffen, T. Cauvet, L. Tickenbrock, P. Ji, S. Diederichs, B. Sargin, G. Kohler, M. Stelljes, E. Puccetti, et al. (2004)
Mol. Cell. Biol. 24, 2890-2904
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Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: Amplification discloses overexpression of APP, ETS2, and ERG genes.
C. D. Baldus, S. Liyanarachchi, K. Mrozek, H. Auer, S. M. Tanner, M. Guimond, A. S. Ruppert, N. Mohamed, R. V. Davuluri, M. A. Caligiuri, et al. (2004)
PNAS 101, 3915-3920
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Mutated SHP and AML in leukemias.
G.-S. Feng (2004)
Blood 103, 1982-1983
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High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia.
H. Harada, Y. Harada, H. Niimi, T. Kyo, A. Kimura, and T. Inaba (2004)
Blood 103, 2316-2324
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The BCR-ABL1 Kinase Bypasses Selection for the Expression of a Pre-B Cell Receptor in Pre-B Acute Lymphoblastic Leukemia Cells.
F. Klein, N. Feldhahn, L. Harder, H. Wang, M. Wartenberg, W.-K. Hofmann, P. Wernet, R. Siebert, and M. Muschen (2004)
J. Exp. Med. 199, 673-685
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The transcriptome of the leukemogenic homeoprotein HOXA9 in human hematopoietic cells.
S. T. Dorsam, C. M. Ferrell, G. P. Dorsam, M. K. Derynck, U. Vijapurkar, D. Khodabakhsh, B. Pau, H. Bernstein, C. M. Haqq, C. Largman, et al. (2004)
Blood 103, 1676-1684
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Large-Scale Identification of Disease Genes Involved in Acute Myeloid Leukemia.
S. J. Erkeland, M. Valkhof, C. Heijmans-Antonissen, A. van Hoven-Beijen, R. Delwel, M. H. A. Hermans, and I. P. Touw (2004)
J. Virol. 78, 1971-1980
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Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse model of t(12;13)(p13;q12) acute myeloid leukemia.
V. P. S. Rawat, M. Cusan, A. Deshpande, W. Hiddemann, L. Quintanilla-Martinez, R. K. Humphries, S. K. Bohlander, M. Feuring-Buske, and C. Buske (2004)
PNAS 101, 817-822
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VWRPY motif-dependent and -independent roles of AML1/Runx1 transcription factor in murine hematopoietic development.
M. Nishimura, Y. Fukushima-Nakase, Y. Fujita, M. Nakao, S. Toda, N. Kitamura, T. Abe, and T. Okuda (2004)
Blood 103, 562-570
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MLL--a gene of interest.
D. C. Arthur (2004)
Blood 103, 6-7
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Butyrates, as a Single Drug, Induce Histone Acetylation and Granulocytic Maturation: Possible Selectivity on Core Binding Factor-Acute Myeloid Leukemia Blasts.
A. Gozzini, E. Rovida, P. Dello Sbarba, S. Galimbert, and V. Santini (2003)
Cancer Res. 63, 8955-8961
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Transcriptional Regulation of ILT Family Receptors.
H. Nakajima, A. Asai, A. Okada, L. Ping, F. Hamajima, T. Sata, and K. Isobe (2003)
J. Immunol. 171, 6611-6620
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Clinical Screening of Gene Rearrangements in Childhood Leukemia by Using a Multiplex Polymerase Chain Reaction-Microarray Approach.
T. V. Nasedkina, V. S. Zharinov, E. A. Isaeva, O. N. Mityaeva, R. N. Yurasov, S. A. Surzhikov, A. Y. Turigin, A. Y. Rubina, A. I. Karachunskii, R. B. Gartenhaus, et al. (2003)
Clin. Cancer Res. 9, 5620-5629
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PU.1 and pRB Interact and Cooperate To Repress GATA-1 and Block Erythroid Differentiation.
N. Rekhtman, K. S. Choe, I. Matushansky, S. Murray, T. Stopka, and A. I. Skoultchi (2003)
Mol. Cell. Biol. 23, 7460-7474
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Clinico-biologic features and treatment outcome of adult pro-B-ALL patients enrolled in the GIMEMA 0496 study: absence of the ALL1/AF4 and of the BCR/ABL fusion genes correlates with a significantly better clinical outcome.
G. Cimino, L. Elia, M. Mancini, L. Annino, B. Anaclerico, P. Fazi, A. Vitale, G. Specchia, F. Di Raimondo, A. Recchia, et al. (2003)
Blood 102, 2014-2020
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Two Distinct Gene Expression Signatures in Pediatric Acute Lymphoblastic Leukemia with MLL Rearrangements.
S. Tsutsumi, T. Taketani, K. Nishimura, X. Ge, T. Taki, K. Sugita, E. Ishii, R. Hanada, M. Ohki, H. Aburatani, et al. (2003)
Cancer Res. 63, 4882-4887
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Survival of acute myeloid leukemia cells requires PI3 kinase activation.
Q. Xu, S.-E. Simpson, T. J. Scialla, A. Bagg, and M. Carroll (2003)
Blood 102, 972-980
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The Runx1 Transcription Factor Inhibits the Differentiation of Naive CD4+ T Cells into the Th2 Lineage by Repressing GATA3 Expression.
O. Komine, K. Hayashi, W. Natsume, T. Watanabe, Y. Seki, N. Seki, R. Yagi, W. Sukzuki, H. Tamauchi, K. Hozumi, et al. (2003)
J. Exp. Med. 198, 51-61
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Cooperation of Cytokine Signaling with Chimeric Transcription Factors in Leukemogenesis: PML-Retinoic Acid Receptor Alpha Blocks Growth Factor-Mediated Differentiation.
V. T. Phan, D. B. Shultz, B.-T. H. Truong, T. J. Blake, A. L. Brown, T. J. Gonda, M. M. Le Beau, and S. C. Kogan (2003)
Mol. Cell. Biol. 23, 4573-4585
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Ewing Tumor Fusion Proteins Block the Differentiation of Pluripotent Marrow Stromal Cells.
E. C. Torchia, S. Jaishankar, and S. J. Baker (2003)
Cancer Res. 63, 3464-3468
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Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation.
A. A. Ferrando, S. A. Armstrong, D. S. Neuberg, S. E. Sallan, L. B. Silverman, S. J. Korsmeyer, and A. T. Look (2003)
Blood 102, 262-268
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Osteoblast-related Transcription Factors Runx2 (Cbfa1/AML3) and MSX2 Mediate the Expression of Bone Sialoprotein in Human Metastatic Breast Cancer Cells.
G. L. Barnes, A. Javed, S. M. Waller, M. H. Kamal, K. E. Hebert, M. Q. Hassan, A. Bellahcene, A. J. van Wijnen, M. F. Young, J. B. Lian, et al. (2003)
Cancer Res. 63, 2631-2637
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