Retroviral vector insertion sites associated with dominant hematopoietic clones mark “stemness” pathways

resulting insertional dominance database (IDDb) shows substantial overlaps with the transcriptome of hematopoietic stem/progenitor cells and the retrovirus-tagged cancer gene database (RTCGD). RVISs preferentially marked genes with high expression in hematopoietic stem/progenitor cells, and Gene Ontology revealed an overrepresentation of genes associated with cell-cycle control, apoptosis signaling, and transcriptional regulation, including major “stemness” pathways. The IDDb forms a powerful resource for the identification of genes that stimulate or transform hematopoietic stem/progenitor cells and is an important reference for vector biosafety studies in human gene therapy. (Blood. 2007;109: 1897-1907) generate direct and indirect pathways. functions

[1]  T. Golub,et al.  Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9 , 2006, Nature.

[2]  A. Iwama,et al.  Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells , 2006, The EMBO journal.

[3]  A. Nienhuis,et al.  Genotoxicity of retroviral integration in hematopoietic cells. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[4]  Clelia Di Serio,et al.  Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration , 2006, Nature Biotechnology.

[5]  M. Okabe,et al.  Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells , 2006, Oncogene.

[6]  Yang Du,et al.  Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1 , 2006, Nature Medicine.

[7]  B. Fehse,et al.  Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors. , 2006, Human gene therapy.

[8]  G. Nucifora,et al.  EVI1 and hematopoietic disorders: history and perspectives. , 2006, Gene.

[9]  C. Bordignon,et al.  Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Hans-Peter Kiem,et al.  Foamy virus vector integration sites in normal human cells , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Bob Löwenberg,et al.  Significance of murine retroviral mutagenesis for identification of disease genes in human acute myeloid leukemia. , 2006, Cancer research.

[12]  N. Copeland,et al.  Sox4 cooperates with Evi1 in AKXD-23 myeloid tumors via transactivation of proviral LTR. , 2006, Blood.

[13]  F. Camargo,et al.  Hematopoietic stem cells do not engraft with absolute efficiencies. , 2006, Blood.

[14]  N. Copeland,et al.  Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells. , 2005, Blood.

[15]  A. Berns,et al.  Retroviral insertional mutagenesis: past, present and future , 2005, Oncogene.

[16]  C. von Kalle,et al.  Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells. , 2005, Blood.

[17]  N. Copeland,et al.  Cooperating cancer-gene identification through oncogenic-retrovirus-induced insertional mutagenesis. , 2005, Blood.

[18]  C. Schwager,et al.  Retroviral Integration Sites Correlate with Expressed Genes in Hematopoietic Stem Cells , 2005, Stem cells.

[19]  Marcel J. T. Reinders,et al.  Maximum significance clustering of oligonucleotide microarrays , 2005, 2005 IEEE Computational Systems Bioinformatics Conference - Workshops (CSBW'05).

[20]  Dick de Ridder,et al.  New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling , 2005, The Journal of experimental medicine.

[21]  C. von Kalle,et al.  Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis. , 2005, Blood.

[22]  B. Fehse,et al.  Clonal Dominance of Hematopoietic Stem Cells Triggered by Retroviral Gene Marking , 2005, Science.

[23]  Lina A. Thoren,et al.  Identification of Flt3+ Lympho-Myeloid Stem Cells Lacking Erythro-Megakaryocytic Potential A Revised Road Map for Adult Blood Lineage Commitment , 2005, Cell.

[24]  J. Coffin,et al.  Relationship between retroviral DNA-integration-site selection and host cell transcription. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Kathryn L. Parsley,et al.  Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector , 2004, The Lancet.

[26]  C. Shaw,et al.  Molecular Signatures of Proliferation and Quiescence in Hematopoietic Stem Cells , 2004, PLoS biology.

[27]  S. Karlsson,et al.  Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells. , 2004, Blood.

[28]  J. V. van Dongen,et al.  Wnt Target Genes Identified by DNA Microarrays in Immature CD34+ Thymocytes Regulate Proliferation and Cell Adhesion1 , 2004, The Journal of Immunology.

[29]  A. Zander,et al.  Dose finding with retroviral vectors: correlation of retroviral vector copy numbers in single cells with gene transfer efficiency in a cell population. , 2003, Blood.

[30]  Cameron S. Osborne,et al.  LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1 , 2003, Science.

[31]  Shawn M. Burgess,et al.  Transcription Start Regions in the Human Genome Are Favored Targets for MLV Integration , 2003, Science.

[32]  Christof von Kalle,et al.  Side effects of retroviral gene transfer into hematopoietic stem cells. , 2003, Blood.

[33]  A. Rimek,et al.  High-level ectopic HOXB4 expression confers a profound in vivo competitive growth advantage on human cord blood CD34+ cells, but impairs lymphomyeloid differentiation. , 2003, Blood.

[34]  William C Hahn,et al.  Rules for making human tumor cells. , 2002, The New England journal of medicine.

[35]  C. von Kalle,et al.  Polyclonal long-term repopulating stem cell clones in a primate model. , 2002, Blood.

[36]  John T. Dimos,et al.  A Stem Cell Molecular Signature , 2002, Science.

[37]  A. Zander,et al.  Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell , 2002, Leukemia.

[38]  Paul Shinn,et al.  HIV-1 Integration in the Human Genome Favors Active Genes and Local Hotspots , 2002, Cell.

[39]  N. Harris,et al.  Bethesda proposals for classification of lymphoid neoplasms in mice. , 2002, Blood.

[40]  J. Downing,et al.  Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice. , 2002, Blood.

[41]  A. Mortellaro,et al.  Correction of ADA-SCID by Stem Cell Gene Therapy Combined with Nonmyeloablative Conditioning , 2002, Science.

[42]  D. Gilliland,et al.  Focus on acute leukemias. , 2002, Cancer cell.

[43]  J. Pipas,et al.  T Antigens of Simian Virus 40: Molecular Chaperones for Viral Replication and Tumorigenesis , 2002, Microbiology and Molecular Biology Reviews.

[44]  C. von Kalle,et al.  Murine Leukemia Induced by Retroviral Gene Marking , 2002, Science.

[45]  A. Fischer,et al.  Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. , 2002, The New England journal of medicine.

[46]  C. von Kalle,et al.  Detection and direct genomic sequencing of multiple rare unknown flanking DNA in highly complex samples. , 2001, Human gene therapy.

[47]  David A. Williams,et al.  Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells , 2000, Nature Medicine.

[48]  C. Buske,et al.  Homeobox genes in leukemogenesis. , 2000, International journal of hematology.

[49]  D. Kohn,et al.  Transduction of pluripotent human hematopoietic stem cells demonstrated by clonal analysis after engraftment in immune-deficient mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[50]  I. Weissman,et al.  Mouse hematopoietic stem cells. , 1991, Blood.

[51]  Christof von Kalle,et al.  and insertional genotoxicity Cell culture assays reveal the importance of retroviral vector design for , 2006 .

[52]  Takeshi Suzuki,et al.  RTCGD: retroviral tagged cancer gene database , 2004, Nucleic Acids Res..

[53]  Anton Berns,et al.  Retroviral insertional mutagenesis: tagging cancer pathways. , 2003, Advances in cancer research.

[54]  Mouse Genome Sequencing Consortium Initial sequencing and comparative analysis of the mouse genome , 2002, Nature.

[55]  K. Cornetta,et al.  Safety issues related to retroviral-mediated gene transfer in humans. , 1991, Human gene therapy.

[56]  What Are All Those Funny Symbols in a Blast Printout? Blast = Basic Local Alignment Search Tool , 2022 .