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This Article Full Text Full Text (PDF) 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 Zeng, X.-X. Articles by Wasserman, R. Search for Related Content PubMed PubMed Citation Articles by Zeng, X.-X. Articles by Wasserman, R. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 92 No. 10 (November 15), 1998: pp. 3529-3536 RAPID COMMUNICATION The Fetal Origin of B-Precursor Leukemia in the Eµ-ret Mouse Xiang-Xing Zeng, Haige Zhang, Richard R. Hardy, and Robert Wasserman From the Division of Oncology, The Children's Hospital of Philadelphia, and Department of Pediatrics, The University of Pennsylvania School of Medicine, Philadelphia, PA; and the Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA. Before the clinical onset of B-precursor lymphoblastic leukemia, Eµ-ret mice have an expansion of late pro-B cells (CD45R+CD43+CD24+BP-1+) within the bone marrow. To characterize the early effects of the transgene product on lymphopoiesis, we initially sequenced the Ig heavy chain (IgH) rearrangements within the late pro-B cells in 24-day-old Eµ-ret and transgene negative mice. In both mouse populations, the IgH rearrangements were polyclonal, predominately nonproductive, and exhibited similar V, D, and J gene usage. However, the frequency of N regions, a marker of postnatal lymphopoiesis, was notably different. At the VD junction, N regions were found in 25 of 25 (100.0%) rearrangements from transgene-negative mice compared with 12 of 36 (33.3%) rearrangements from Eµ-ret mice. At the DJ junction, N regions were found in 21 of 25 (84.0%) rearrangements from transgene negative mice compared with 4 of 36 (11.1%) rearrangements from Eµ-ret mice. Subsequently, we sequenced the clonal IgH rearrangements from 9 leukemias that developed in 10-to 38-week-old mice and found that 7 leukemias had a least 1 rearrangement that lacked N regions at the DJ junction. In addition, V replacement events were observed in the 1 leukemia studied in detail. Terminal deoxynucleotidyl transferase, the enzyme responsible for N region addition, was expressed at markedly lower levels in late pro-B cells from 7- to 10-day-old Eµ-ret mice compared with transgene-negative mice. Examination of fetal lymphopoiesis in Eµ-ret mice identified a relative increase in early (CD45R+CD43+CD24+BP-1) and late pro-B cells and a decrease in more differentiated CD43 B-lineage cells. Fetal early pro-B cells from Eµ-ret mice proliferated threefold to fivefold greater but differentiated to a lesser extent than those from transgene negative mice when cultured in vitro with interleukin-7. These data suggest that the B precursor leukemias in adult Eµ-ret mice arise from the progeny of pro-B cells generated in utero. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. I. Brown, J. Fang, K. Alcorn, R. Barr, J. M. Kim, R. Wasserman, and S. A. Grupp Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect that is modulated by IL-7-mediated signaling PNAS, December 9, 2003; 100(25): 15113 - 15118. [Abstract] [Full Text] [PDF]

	Copyright © 1998 by American Society of Hematology         Online ISSN: 1528-0020