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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3932-3939. Prepublished online as a Blood First Edition Paper on August 18, 2005; DOI 10.1182/blood-2005-03-1113. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1113v1 106/12/3932    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 Du, Y. Articles by Copeland, N. G. Search for Related Content PubMed PubMed Citation Articles by Du, Y. Articles by Copeland, N. G. Related Collections Hematopoiesis and Stem Cells Neoplasia Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells Yang Du, Nancy A. Jenkins, and Neal G. Copeland From the Mouse Cancer Genetics Program, National Cancer Institute, Center for Cancer Research, Frederick, MD. Retroviruses can induce hematopoietic disease via insertional mutagenesis of cancer genes and provide valuable molecular tags for cancer gene discovery. Here we show that insertional mutagenesis can also identify genes that promote the immortalization of hematopoietic cells, which normally have only limited self-renewal. Transduction of mouse bone marrow cells with replication-incompetent murine stem cell virus (MSCV) expressing only neo, followed by serial passage in liquid culture containing stem cell factor (SCF) and interleukin-3 (IL-3), produced immortalized immature myeloid cell lines with neutrophil and macrophage differentiation potential in about 50% of the infected cultures. More than half of the lines have MSCV insertions at Evi1 or Prdm16. These loci encode transcription factor homologs and are validated human myeloid leukemia genes. Integrations are located in intron 1 or 2, where they promote expression of truncated proteins lacking the PRDI-BF1-RIZ1 homologous (PR) domain, similar to what is observed in human leukemias with EVI1 or PRDM16 mutations. Evi1 overexpression alone appears sufficient to immortalize immature myeloid cells and does not seem to require any other cooperating mutations. 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