Murine Leukemia Induced by Retroviral Gene Marking

  title={Murine Leukemia Induced by Retroviral Gene Marking},
  author={Zhixiong Li and Jochen Düllmann and Bernd Schiedlmeier and Manfred Schmidt and Christof von Kalle and Johann Meyer and Martin Forster and Carol Stocking and Anke Wahlers and Oliver Frank and Wolfram Ostertag and Klaus Kühlcke and H. G. Eckert and Boris Fehse and Christopher Baum},
  pages={497 - 497}
Somatic gene transfer is a promising therapeutic strategy, but it may also evoke new types of side effects related to genetic damage or transgene activity. Retroviral vectors, the best tool currently available for stable genetic modification, integrate at random positions in the cellular genome. The 

Lentiviral vector integration sites in human NOD/SCID repopulating cells

Recent observations of insertional mutagenesis in preclinical and clinical settings emphasize the relevance of investigating comprehensively the spectrum of integration sites targeted by specific

Gene therapy for immunodeficiency diseases.

Primary immunodeficiency diseases represent good targets for hematopoietic stem cell-targeted gene therapy and new advances in the technology of gene transfer should further promote gene therapy as a safe and effective therapeutic strategy of immunodficiency diseases.

Functional analysis of gammaretroviral vector transduction by quantitative PCR

In a clinical setting of gene therapy, quantitative methods are required to determine recombinant viral titres and transgene mRNA expression, avoiding the use of reporter genes.

Chance or necessity? Insertional mutagenesis in gene therapy and its consequences.

A novel approach for gene therapy: engraftment of fibroblasts containing the artificial chromosome expression system at the site of inflammation

Gene transfer might provide a more efficient delivery system for genes encoding therapeutic proteins in order to achieve therapeutic levels of anti‐rheumatic drugs in the joints.

Reducing the genotoxic potential of retroviral vectors.

In this chapter, various strategies are described to reduce the associated risks of retroviral genomic integration, including deletion of strong transcriptional enhancer-promoter elements in the Retroviral long terminal repeats, flanking the retroViral transcriptional unit with enhancer blocking sequences and designing vectors with improved RNA 3' end processing.

The yin and yang of stem cell gene therapy: insights into hematopoiesis, leukemogenesis, and gene therapy safety.

  • C. Dunbar
  • Biology, Medicine
    Hematology. American Society of Hematology. Education Program
  • 2007
Investigators are now focused on retaining the clinical potential of integrating vectors while decreasing the risk of insertional mutagenesis.

Clonal Dominance of Hematopoietic Stem Cells Triggered by Retroviral Gene Marking

It is demonstrated that retroviral integrations themselves may trigger nonmalignant clonal expansion in murine long-term hematopoiesis and have major implications for diagnostic gene marking and the discovery of genes regulating stem cell turnover.

Characterization of a semi‐replicative gene delivery system allowing propagation of complementary defective retroviral vectors

A semi‐replication‐competent retroviral vector system is developed to enhance both their integral safety and their transgene capacity.

Insertional Mutagenesis in Hematopoietic Cells: Lessons Learned from Adverse Events in Clinical Gene Therapy Trials

From an early stage in the development of retroviral vectors for gene therapy applications, there has been a concern that recombinant vectors could elicit cellular transformation by altering



HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia.

The data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.

Distinct classes of factor-independent mutants can be isolated after retroviral mutagenesis of a human myeloid stem cell line.

A tissue culture system using the human, growth factor-dependent, hematopoietic precursor cell line TF-1 is developed that permits the use of retroviral vectors to induce a large increase in the mutation frequency to growth factor independence and thus the isolation of many mutants.

Influence of multiplicity of infection and protein stability on retroviral vector-mediated gene expression in hematopoietic cells

An important and differentiation-dependent contribution of protein half-life to the expression of retroviral vectors in hematopoietic cells is revealed, which establishes d2EGFP as a more accurate reporter for determination of vector transcription, and suggests that preclinical data obtained under conditions of high transduction rates or with vectors expressing stable reporter proteins require careful interpretation.

Identification and Characterization of an Activating TrkA Deletion Mutation in Acute Myeloid Leukemia

This report is the initial demonstration that deletions within TrkA may play a role in human cancers, and is the first to indicate mutations in TrKA may contribute to leukemogenesis.

The uniqueness of being a neurotrophin receptor

Detection and direct genomic sequencing of multiple rare unknown flanking DNA in highly complex samples.

EpTS/LM-PCR enables studies of retro- and lentiviral integration, viral vector tracking in gene therapy, insertional mutagenesis, transgene integration, and direct genomic sequencing that until now have been difficult or impossible to perform.