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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4369-4376. Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-05-1762. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1762v1 102/13/4369    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mulloy, J. C. Articles by Nimer, S. D. Search for Related Content PubMed PubMed Citation Articles by Mulloy, J. C. Articles by Nimer, S. D. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element James C. Mulloy, Jorg Cammenga, Francisco J. Berguido, Kaida Wu, Ping Zhou, Raymond L. Comenzo, Suresh Jhanwar, Malcolm A. S. Moore, and Stephen D. Nimer From the Laboratory of Molecular Aspects of Hematopoiesis and the Laboratory of Developmental Hematopoiesis, Sloan-Kettering Institute, New York, NY; and the Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY. Hematopoiesis is a complex process involving hematopoietic stem cell (HSC) self-renewal and lineage commitment decisions that must continue throughout life. Establishing a reproducible technique that allows for the long-term ex vivo expansion of human HSCs and maintains self-renewal and multipotential differentiation will allow us to better understand these processes, and we report the ability of the leukemia-associated AML1-ETO fusion protein to establish such a system. AML1-ETO-transduced human CD34+ hematopoietic cells routinely proliferate in liquid culture for more than 7 months, remain cytokine dependent for survival and proliferation, and demonstrate self-renewal of immature cells that retain both lymphoid and myeloid potential in vitro. These cells continue to express the CD34 cell surface marker and have ongoing telomerase activity with maintenance of telomere ends, however they do not cause leukemia in nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice. Identification of the signaling pathways that are modulated by AML1-ETO and lead to the self-renewal of immature human progenitor cells may assist in identifying compounds that can efficiently expand human stem and progenitor cells ex vivo. (Blood. 2003; 102:4369-4376) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Dayyani, J. Wang, J.-R. J. Yeh, E.-Y. Ahn, E. Tobey, D.-E. Zhang, I. D. Bernstein, R. T. Peterson, and D. A. Sweetser Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival Blood, April 15, 2008; 111(8): 4338 - 4347. [Abstract] [Full Text] [PDF] X. Zhao, V. Jankovic, A. Gural, G. Huang, A. Pardanani, S. Menendez, J. Zhang, R. Dunne, A. Xiao, H. Erdjument-Bromage, et al. 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[Abstract] [Full Text] [PDF] M. Wunderlich, O. Krejci, J. Wei, and J. C. Mulloy Human CD34+ cells expressing the inv(16) fusion protein exhibit a myelomonocytic phenotype with greatly enhanced proliferative ability Blood, September 1, 2006; 108(5): 1690 - 1697. [Abstract] [Full Text] [PDF] A. Takeda, C. Goolsby, and N. R. Yaseen NUP98-HOXA9 Induces Long-term Proliferation and Blocks Differentiation of Primary Human CD34+ Hematopoietic Cells. Cancer Res., July 1, 2006; 66(13): 6628 - 6637. [Abstract] [Full Text] [PDF] J. Cammenga, S. Horn, U. Bergholz, G. Sommer, P. Besmer, W. Fiedler, and C. Stocking Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate Blood, December 1, 2005; 106(12): 3958 - 3961. [Abstract] [Full Text] [PDF] L. Stepanova and B. P. Sorrentino A limited role for p16Ink4a and p19Arf in the loss of hematopoietic stem cells during proliferative stress Blood, August 1, 2005; 106(3): 827 - 832. [Abstract] [Full Text] [PDF] J. C. Mulloy, V. Jankovic, M. Wunderlich, R. Delwel, J. Cammenga, O. Krejci, H. Zhao, P. J. M. Valk, B. Lowenberg, and S. D. Nimer AML1-ETO fusion protein up-regulates TRKA mRNA expression in human CD34+ cells, allowing nerve growth factor-induced expansion PNAS, March 15, 2005; 102(11): 4016 - 4021. [Abstract] [Full Text] [PDF] Y.-Y. Wang, G.-B. Zhou, T. Yin, B. Chen, J.-Y. Shi, W.-X. Liang, X.-L. Jin, J.-H. You, G. Yang, Z.-X. Shen, et al. AML1-ETO and C-KIT mutation/overexpression in t(8;21) leukemia: Implication in stepwise leukemogenesis and response to Gleevec PNAS, January 25, 2005; 102(4): 1104 - 1109. [Abstract] [Full Text] [PDF] J. D. Licht and D. W. Sternberg The Molecular Pathology of Acute Myeloid Leukemia Hematology, January 1, 2005; 2005(1): 137 - 142. [Abstract] [Full Text] [PDF] M. Yan, S. A. Burel, L. F. Peterson, E. Kanbe, H. Iwasaki, A. Boyapati, R. Hines, K. Akashi, and D.-E. Zhang From the Cover: Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development PNAS, December 7, 2004; 101(49): 17186 - 17191. [Abstract] [Full Text] [PDF] T. S. Fenske, G. Pengue, V. Mathews, P. T. Hanson, S. E. Hamm, N. Riaz, and T. A. Graubert Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative disorder in mice PNAS, October 19, 2004; 101(42): 15184 - 15189. [Abstract] [Full Text] [PDF]

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