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Blood, 20 August 2009, Vol. 114, No. 8, pp. 1576-1584. Prepublished online as a Blood First Edition Paper on June 8, 2009; DOI 10.1182/blood-2009-03-212704. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2009-03-212704v1 114/8/1576    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 CrossRef Google Scholar Articles by Ren, M. Articles by Cowell, J. K. PubMed PubMed Citation Articles by Ren, M. Articles by Cowell, J. K. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Genetic fingerprinting of the development and progression of T-cell lymphoma in a murine model of atypical myeloproliferative disorder initiated by the ZNF198–fibroblast growth factor receptor-1 chimeric tyrosine kinase Mingqiang Ren1, Xiurong Li2, and John K. Cowell1 1 Medical College of Georgia Cancer Center, Augusta; and 2 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY A mouse model of human ZNF198–fibroblast growth factor receptor-1 (FGFR1) stem cell leukemia lymphoma has been developed to investigate mechanisms of oncogenesis and progression. Using array-based comparative genomic hybridization, we followed disease progression after serial transplantation of ZNF198-FGFR1–transformed stem cells that give rise to a distinct myeloproliferative disorder and T-lymphoblastic leukemia. A consistent, frequently homozygous, chr14:53880459-55011545 deletion, containing the T-cell receptor and genes, was identified in the bone marrow, spleen, and lymph nodes in all cases. The absence of cell-surface T-cell receptor in tumor cells precludes CD3 recruitment, resulting in loss of a functional T-cell receptor complex, supporting the idea that prevention of maturation of CD4+/CD8+ double-positive immature T cells is important in ZNF198-FGFR1 disease development. Up-regulation of the B-cell line 2, interleukin 7 receptor and interleuking 2 receptor prosurvival genes in these undifferentiated tumor precursor cells suggests one mechanism that allows them to escape apoptosis in the thymus. Thus, we have defined an important event in the process of ZNF198-FGFR1–induced T-cell leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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