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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4285-4293. Prepublished online as a Blood First Edition Paper on February 12, 2004; DOI 10.1182/blood-2003-09-3192. This Article Full Text (PDF) All Versions of this Article: 2003-09-3192v1 103/11/4285    most recent Alert me when this article is cited Alert me if a correction is posted 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 Thanopoulou, E. Articles by Eaves, C. Search for Related Content PubMed PubMed Citation Articles by Thanopoulou, E. Articles by Eaves, C. Related Collections Related Letter in Blood Online Social Bookmarking                   What's this? Submitted September 16, 2003 Accepted February 4, 2004 Engraftment of NOD/SCID-2 microglobulin null mice with multi-lineage neoplastic cells from patients with myelodysplastic syndrome Eleni Thanopoulou, Johanne Cashman, Theodora Kakagianne, Allen Eaves, Nicholas Zoumbos, and Connie Eaves* Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada * Corresponding author; email: ceaves{at}bccrc.ca. The development of immunodeficient mouse-xenograft models has greatly facilitated the investigation of some human hematopoietic malignancies, but application of this approach to the myelodysplastic syndromes (MDS) has proven difficult. We now show that cells from most MDS patients (including all subtypes) repopulate nonobese diabetic- scid/scid-2microglobulin null (NOD/SCID-2m-/-) mice at least transiently and produce abnormal differentiation patterns in this model. Normal marrow transplants initially produce predominantly erythroid cells and later predominantly B-lymphoid cells in these mice, whereas most MDS samples produced predominantly granulopoietic cells. In 4/4 MDS cases, the regenerated cells showed the same clonal markers (trisomy 8, n=3 and 5q-, n=1) as the original sample and, in one instance, regenerated trisomy 8+ B-lymphoid as well as myeloid cells were identified. Interestingly, the enhanced growth of normal marrow obtained in NOD/SCID-2m-/- mice engineered to produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor was seen only with 1 of 7 MDS samples. These findings support the concept that human MDS originates in a transplantable multi-lineage hematopoietic stem cell whose genetic alteration may affect patterns of differentiation and responsiveness to hematopoietic growth factors. They also demonstrate the potential of this new murine xenotransplant model for future investigations of MDS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Engraftment of distinct clonal MDS-derived hematopoietic precursors in NOD/SCID-2-microglobulin-deficient mice after intramedullary transplantation of hematopoietic and stromal cells Daniella M. Bahia Kerbauy, Vladimir Lesnikov, Beverly Torok-Storb, Eileen Bryant, and H. Joachim Deeg Blood 2004 104: 2202-2203. [Full Text] [PDF] This article has been cited by other articles: A. Tefferi and J. W. Vardiman Myelodysplastic Syndromes N. Engl. J. Med., November 5, 2009; 361(19): 1872 - 1885. [Full Text] [PDF] D. T. Starczynowski, S. Vercauteren, A. Telenius, S. Sung, K. Tohyama, A. Brooks-Wilson, J. J. Spinelli, C. J. Eaves, A. C. Eaves, D. E. Horsman, et al. High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival Blood, October 15, 2008; 112(8): 3412 - 3424. [Abstract] [Full Text] [PDF] Y. J. Chung, C. W. Choi, C. Slape, T. Fry, and P. D. Aplan Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell PNAS, September 16, 2008; 105(37): 14088 - 14093. [Abstract] [Full Text] [PDF] S. D. Nimer MDS: A Stem Cell Disorder--But What Exactly Is Wrong with the Primitive Hematopoietic Cells in This Disease? Hematology, January 1, 2008; 2008(1): 43 - 51. [Abstract] [Full Text] [PDF] L. Nilsson, P. Eden, E. Olsson, R. Mansson, I. Astrand-Grundstrom, B. Strombeck, K. Theilgaard-Monch, K. Anderson, R. Hast, E. Hellstrom-Lindberg, et al. The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes Blood, October 15, 2007; 110(8): 3005 - 3014. [Abstract] [Full Text] [PDF] R. Bhatia, K. Van Heijzen, A. Palmer, A. Komiya, M. L. Slovak, K. L. Chang, H. Fung, A. Krishnan, A. Molina, A. Nademanee, et al. Longitudinal Assessment of Hematopoietic Abnormalities After Autologous Hematopoietic Cell Transplantation for Lymphoma J. Clin. Oncol., September 20, 2005; 23(27): 6699 - 6711. [Abstract] [Full Text] [PDF] M. Xu, E. Bruno, J. Chao, H. Ni, V. Lindgren, R. Nunez, N. Mahmud, G. Finazzi, S. M. Fruchtman, U. Popat, et al. The constitutive mobilization of bone marrow-repopulating cells into the peripheral blood in idiopathic myelofibrosis Blood, February 15, 2005; 105(4): 1699 - 1705. [Abstract] [Full Text] [PDF] D. M. B. Kerbauy, V. Lesnikov, B. Torok-Storb, E. Bryant, and H. J. Deeg Engraftment of distinct clonal MDS-derived hematopoietic precursors in NOD/SCID-{beta}2-microglobulin-deficient mice after intramedullary transplantation of hematopoietic and stromal cells Blood, October 1, 2004; 104(7): 2202 - 2203. [Full Text] [PDF]

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