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Blood, 15 July 2006, Vol. 108, No. 2, pp. 669-677. Prepublished online as a Blood First Edition Paper on March 21, 2006; DOI 10.1182/blood-2005-08-3498. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-08-3498v1 108/2/669    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 Chen, W. Articles by Kersey, J. H. Search for Related Content PubMed PubMed Citation Articles by Chen, W. Articles by Kersey, J. H. Related Collections Neoplasia Oncogenes and Tumor Suppressors Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy Weili Chen, Quanzhi Li, Wendy A. Hudson, Ashish Kumar, Nicole Kirchhof, and John H. Kersey From the Cancer Center, University of Minnesota, Minneapolis; Department of Pediatrics, University of Minnesota, Minneapolis; Veterinary Diagnostic Lab & Cancer Center Histopathology, University of Minnesota, St Paul; and Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis. The 2 most frequent human MLL hematopoietic malignancies involve either AF4 or AF9 as fusion partners; each has distinct biology but the role of the fusion partner is not clear. We produced Mll-AF4 knock-in (KI) mice by homologous recombination in embryonic stem cells and compared them with Mll-AF9 KI mice. Young Mll-AF4 mice had lymphoid and myeloid deregulation manifest by increased lymphoid and myeloid cells in hematopoietic organs. In vitro, bone marrow cells from young mice formed unique mixed pro-B lymphoid (B220+CD19+CD43+sIgM–, PAX5+, TdT+, IgH rearranged)/myeloid (CD11b/Mac1+, c-fms+, lysozyme+) colonies when grown in IL-7– and Flt3 ligand-containing media. Mixed lymphoid/myeloid hyperplasia and hematologic malignancies (most frequently B-cell lymphomas) developed in Mll-AF4 mice after prolonged latency; long latency to malignancy indicates that Mll-AF4–induced lymphoid/myeloid deregulation alone is insufficient to produce malignancy. In contrast, young Mll-AF9 mice had predominately myeloid deregulation in vivo and in vitro and developed myeloid malignancies. The early onset of distinct mixed lymphoid/myeloid lineage deregulation in Mll-AF4 mice shows evidence for both "instructive" and "noninstructive" roles for AF4 and AF9 as partners in MLL fusion genes. The molecular basis for "instruction" and secondary cooperating mutations can now be studied in our Mll-AF4 model. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Alert and sniffy-nosed about Mll-AF4? Mel Greaves and C. W. Eric So Blood 2006 108: 416-417. [Full Text] [PDF] This article has been cited by other articles: B. W. Robinson, N.-K. V. Cheung, C. P. Kolaris, S. C. Jhanwar, J. K. Choi, N. Osheroff, and C. A. Felix Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome Blood, April 1, 2008; 111(7): 3802 - 3812. [Abstract] [Full Text] [PDF] H. Liu, E. H.-Y. Cheng, and J. J.-D. Hsieh Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions Genes & Dev., October 1, 2007; 21(19): 2385 - 2398. [Abstract] [Full Text] [PDF] F. Barabe, J. A. Kennedy, K. J. Hope, and J. E. Dick Modeling the Initiation and Progression of Human Acute Leukemia in Mice Science, April 27, 2007; 316(5824): 600 - 604. [Abstract] [Full Text] [PDF]

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