Research Topics
Genomes and Genes | C BaumSummaryAffiliation: Hannover Medical School Country: Germany Publications
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Publications
Gene therapy targeting hematopoietic cells: better not leave it to chanceChristopher Baum
Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
Acta Haematol 110:107-9. 2003..Interestingly, correction of genetic disorders by homologous gene repair in defined stem cell clones is on the horizon, but far from being available for clinical use...
Side effects of retroviral gene transfer into hematopoietic stem cellsChristopher Baum
Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
Blood 101:2099-114. 2003....
Mutagenesis by retroviral transgene insertion: risk assessment and potential alternativesChristopher Baum
Department of Hematology and Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
Curr Opin Mol Ther 5:458-62. 2003..Ongoing research aims to reduce side effects of therapeutic transgene insertion by dose optimization and definition of contributing risk factors...
Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectorsChristopher Baum
Experimental Cell Therapy, Department of Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany
Hum Gene Ther 17:253-63. 2006..Improving vector design appears to be the most straightforward approach to increase safety, provided all relevant cofactors are considered...
Insertional mutagenesis in gene therapy and stem cell biologyChristopher Baum
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Curr Opin Hematol 14:337-42. 2007..This review summarizes novel studies of underlying mechanisms; these studies have demonstrated the possibility of improved gene vector biosafety and generated new insights into stem cell biology...
[Gene therapy of SCID-X1]C Baum
Medizinische Hochschule Hannover, BRD
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 50:1507-17. 2007..In future clinical trials, improved vector technology in combination with other protocol modifications may reduce the risk of this side effect...
Concise review: managing genotoxicity in the therapeutic modification of stem cellsChristopher Baum
Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany
Stem Cells 29:1479-84. 2011..d) Improved approaches for the genetic modification of stem cells can address all critical steps in the origin and growth control of mutants...
[Advancement of the medical doctorate]C Baum
Abt Experimentelle Hämatologie, Medizinische Hochschule Hannover, 30625 Hannover
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 52:856-61. 2009..Evaluating the achievements and career paths of the trainees will contribute to the successful integration of research work in an efficiency-oriented clinical environment...
Parachuting in the epigenome: the biology of gene vector insertion profiles in the context of clinical trialsChristopher Baum
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
EMBO Mol Med 3:75-7. 2011..This explains the great interest ina deeper understanding of retroviral vector–host interactions in the therapeutic setting of SCID-ADA...
Retrovirus vectors: toward the plentivirus?Christopher Baum
Department of Experimental Hematology, Hannover Medical School, D 30625 Hannover, Germany
Mol Ther 13:1050-63. 2006..Many of the above goals will require the inclusion of nonretroviral components into vector particles or transgenes...
Towards hematopoietic stem cell-mediated protection against infection with human immunodeficiency virusA Schambach
Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Hannover, Germany
Gene Ther 13:1037-47. 2006..These data encourage further investigations in large animal models and clinical trials...
Leukemia induction after a single retroviral vector insertion in Evi1 or Prdm16U Modlich
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Leukemia 22:1519-28. 2008..Our study also shows that insertional mutagenesis is required for leukemia induction by IL2RG vectors, a risk to be addressed by improved vector design...
Overcoming promoter competition in packaging cells improves production of self-inactivating retroviral vectorsA Schambach
Department of Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
Gene Ther 13:1524-33. 2006..This study introduces a new generation of efficient gammaretroviral SIN vectors as a platform for further optimizations of retroviral vector performance...
Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cellZ Li
Experimental Cell Therapy, Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
Leukemia 16:1655-63. 2002....
Woodchuck hepatitis virus post-transcriptional regulatory element deleted from X protein and promoter sequences enhances retroviral vector titer and expressionA Schambach
Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Hannover, Germany
Gene Ther 13:641-5. 2006..Furthermore, the X protein promoter could be deleted without compromising the enhancement of vector titers and transgene expression. Such a modified PRE sequence appears useful for future vector design...
Mechanisms controlling titer and expression of bidirectional lentiviral and gammaretroviral vectorsT Maetzig
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Gene Ther 17:400-11. 2010..This allowed for the tracking of chemoprotected and recombined cells by fluorescence marker expression...
Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesisUte Modlich
Department of Hematology, Hemostaseology and Oncology, Institute of Cellular and Molecular Pathology, Hannover Medical School, Germany
Blood 105:4235-46. 2005..On the basis of these findings, we suggest the use of preclinical dose-escalation studies to define a therapeutic index for retroviral transgene delivery...
Gene therapy for inherited disorders of haematopoietic cellsChristoph Klein
Experimental Hematology and Oncology, Department of Pediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
Hematol J 5:103-11. 2004....
Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicityUte Modlich
Department of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
Blood 108:2545-53. 2006..Additional modifications of SIN vectors may further increase safety. Improved cell-culture assays will likely play an important role in the evaluation of insertional mutagenesis...
Vector design for expression of O6-methylguanine-DNA methyltransferase in hematopoietic cellsAxel Schambach
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
DNA Repair (Amst) 6:1187-96. 2007..We conclude that the appropriate design of expression vectors and MGMT protein features will be crucial for the long-term prospects of this promising selection principle...
Cell-intrinsic and vector-related properties cooperate to determine the incidence and consequences of insertional mutagenesisOlga S Kustikova
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Mol Ther 17:1537-47. 2009..Furthermore, our study offers perspectives for refinement of animal experiments in the assessment of vector-related genotoxicity...
Physiological promoters reduce the genotoxic risk of integrating gene vectorsDaniela Zychlinski
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Mol Ther 16:718-25. 2008..In this manner, the insertional biosafety of therapeutic gene vectors can be greatly enhanced and proactively evaluated in sensitive cell-based assays...
Chance or necessity? Insertional mutagenesis in gene therapy and its consequencesChristopher Baum
Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
Mol Ther 9:5-13. 2004..Based on these considerations, we propose approaches to risk prediction and prevention...
Predictable and efficient retroviral gene transfer into murine bone marrow repopulating cells using a defined vector doseZhixiong Li
Experimental Cell Therapy, Department of Hematology and Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
Exp Hematol 31:1206-14. 2003..This protocol may help to improve the predictive value of preclinical efficiency/toxicity studies for gene therapeutic interventions and basic research...
Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, deltaTrkAJ Meyer
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Leukemia 21:2171-80. 2007....
LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropeniaJulia Skokowa
Department of Pediatric Hematology and Oncology Carl Neuberg Str 1, 30625 Hannover, Germany
Nat Med 12:1191-7. 2006..These observations indicate that LEF-1 is an instructive factor regulating neutrophilic granulopoiesis whose absence plays a critical role in the defective maturation program of myeloid progenitors in individuals with CN...
Retroviral vector insertion sites associated with dominant hematopoietic clones mark "stemness" pathwaysOlga S Kustikova
Department of Experimental Hematology, Hannover Medical School, Germany
Blood 109:1897-907. 2007..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...
Insertional mutagenesis by replication-deficient retroviral vectors encoding the large T oncogeneZhixiong Li
Department of Experimental Hematology, OE6960, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
Ann N Y Acad Sci 1106:95-113. 2007..These findings have important implications for the use of retroviral transgenesis in cancer research, and the expression of signaling genes in somatic gene therapy...
High-affinity neurotrophin receptors and ligands promote leukemogenesisZhixiong Li
Department ofExperimental Hematology, Hannover Medical School, Hannover, Germany
Blood 113:2028-37. 2009..Moreover, activation of TRKs was important for survival of both human and murine leukemic cells. Our findings suggest that TRKs play an important role in leukemogenesis and may serve as a new drug target...
Control of self-renewal and differentiation of hematopoietic stem cells: HOXB4 on the thresholdHannes Klump
Department of Hematology, Hemostaseology, and Oncology, Laboratory of Experimental Cell Therapy LECT, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
Ann N Y Acad Sci 1044:6-15. 2005..Indeed, existing evidence suggests that dosage effects of ectopically expressed transcription factors may be more the rule than an exception...
HOXB4's road map to stem cell expansionBernhard Schiedlmeier
Department of Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
Proc Natl Acad Sci U S A 104:16952-7. 2007..In summary, our results strongly suggest that HOXB4 modulates the response of HSCs to multiple extrinsic signals in a concerted manner, thereby shifting the balance toward stem cell self-renewal...
Generation and genetic modification of induced pluripotent stem cellsAxel Schambach
Hannover Medical School, Department of Experimental Hematology, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
Expert Opin Biol Ther 10:1089-103. 2010..iPSCs represent an almost inexhaustible source of cells for targeted differentiation into somatic effector cells and hence are likely to be invaluable for therapeutic applications and disease-related research...
Safety and efficacy in retrovirally modified haematopoietic cell therapyZhixiong Li
Department of Haematology, Haemostaseology and Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
Best Pract Res Clin Haematol 17:493-503. 2004....
Self-inactivating alpharetroviral vectors with a split-packaging designJulia D Suerth
Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
J Virol 84:6626-35. 2010..We demonstrate proof of principle for the versatility of alpharetroviral SIN vectors for the genetic modification of murine and human hematopoietic cells at a low multiplicity of infection...
Preventing and exploiting the oncogenic potential of integrating gene vectorsUte Modlich
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
J Clin Invest 119:755-8. 2009..These findings will inform future vector design with the goal of limiting genotoxicity for gene therapy or increasing genotoxicity for protooncogene discovery...
Gene therapy of MPL deficiency: challenging balance between leukemia and pancytopeniaDaniel C Wicke
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Mol Ther 18:343-52. 2010..Mice that received BM cells expressing Mpl from the Mpl promoter were free of any previously observed adverse reactions...
Clinical application of lentiviral vectors - concepts and practiceAxel Schambach
Department of Experimental Hematology, Hannover Medical School, Germany
Curr Gene Ther 8:474-82. 2008..Some additional applications that are expected to lead to the initiation of clinical trials in the near future are also discussed...
Improving transcriptional termination of self-inactivating gamma-retroviral and lentiviral vectorsAxel Schambach
1Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Mol Ther 15:1167-73. 2007..Importantly, the 2xSV USE was superior to the wPRE in suppressing transcriptional read-through, improving not only vector efficiency but potentially also biosafety...
I could die for you: new prospects for suicide in gene therapyChristopher Baum
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Mol Ther 15:848-9. 2007
Expression of the p75 neurotrophin receptor in acute leukaemiaGernot Beutel
Department of Haematology, Haemostasis and Oncology, Hannover Medical School, Hannover, Germany
Br J Haematol 131:67-70. 2005..These results support further detailed analyses of neurotrophin receptors and downstream signalling pathways in haematological malignancies...
Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectorsUte Modlich
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Mol Ther 17:1919-28. 2009..Mechanistic studies support the conclusion that enhancer-mediated gene activation is the major cause for insertional transformation of hematopoietic cells, opening rational strategies for risk prevention...
Epidermal growth factor improves lentivirus vector gene transfer into primary mouse hepatocytesM Rothe
1 Department of gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany 2 Department of Experimental Hematology, Hannover Medical School, Hannover, Germany 3 TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Hannover Medical School MHH and the Helmholtz Centre for Infection Research HZI, Hannover, Germany
Gene Ther 19:425-34. 2012..Our findings highlight the importance of EGF for efficient LV transduction of primary hepatocytes in culture and should facilitate studies of LV gene transfer in mouse models of monogenetic liver disease...
Retroviral integration site analysis in hematopoietic stem cellsOlga S Kustikova
Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
Methods Mol Biol 430:255-67. 2008..In murine bone marrow transplantation models, we have shown that this method is very useful to analyze the impact of retroviral insertion sites on both malignant and benign clonal dominance of individual repopulating HSC...
Cellular restriction of retrovirus particle-mediated mRNA transferMelanie Galla
Department of Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
J Virol 82:3069-77. 2008..Our data imply that retroviral nucleic acids become accessible to host factors, including ribosomes, as a result of particle remodeling during cytoplasmic trafficking...
Inhibition of human immunodeficiency virus type 1 entry in cells expressing gp41-derived peptidesMarc Egelhofer
Institute for Biomedical Research Georg-Speyer-Haus, Frankfurt a. M. Medizinische Hochschule Hannover, Hannover, Germany
J Virol 78:568-75. 2004..Preclinical toxicity and efficacy studies of this antiviral vector have been completed, and clinical trials are in preparation...
Lentiviral vectors pseudotyped with murine ecotropic envelope: increased biosafety and convenience in preclinical researchAxel Schambach
Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Germany
Exp Hematol 34:588-92. 2006..High efficiency and superior biosafety in combination with convenient handling will certainly boost the potential applicability of this important vector system...
Multiplexing RMCE: versatile extensions of the Flp-recombinase-mediated cassette-exchange technologySoeren Turan
Hannover Medical School OE6960 Experimental Hematology, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
J Mol Biol 402:52-69. 2010..e., the simultaneous exchange of two separate target cassettes in a given cell)...
Murine leukemia virus regulates alternative splicing through sequences upstream of the 5' splice siteJanine Kraunus
Department of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany
J Biol Chem 281:37381-90. 2006..Together, these findings suggest that sequences upstream of the 5' splice site play an important role in splice regulation of simple retroviruses, directly or indirectly attenuating the efficiency of splicing...
Gene therapy: X-SCID transgene leukaemogenicityAdrian J Thrasher
Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
Nature 443:E5-6; discussion E6-7. 2006..Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated...
Murine leukemia induced by retroviral gene markingZhixiong Li
Heinrich-Pette-Institute, D-20251 Hamburg, Germany
Science 296:497. 2002
Genetic protection of repopulating hematopoietic cells with an improved MDR1-retrovirus allows administration of intensified chemotherapy following stem cell transplantation in miceAlexander Carpinteiro
Department of Cell and Virus Genetics, Heinrich-Pette-Institute, Hamburg, Germany
Int J Cancer 98:785-92. 2002..Our mouse model, mimicking clinically achievable gene transfer rates, thus suggests that bone marrow chemoprotection may widen the therapeutic window and permit an earlier onset of post-transplantation chemotherapy...
Resistance of mature T cells to oncogene transformationSebastian Newrzela
Georg Speyer Haus, Institute for Biomedical Research, Frankfurt, Germany
Blood 112:2278-86. 2008..Thus, our data provide direct evidence that mature T cells are less prone to transformation than hematopoietic progenitor cells...
The message is sufficient: towards nontoxic delivery of endonucleasesChristopher Baum
Mol Ther 13:461-2. 2006
HOXB4 inhibits cell growth in a dose-dependent manner and sensitizes cells towards extrinsic cuesElke Will
Department of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
Cell Cycle 5:14-22. 2006..Based on these results we propose that HOXB4 affects cell growth in a dose-dependent manner by sensitizing cells towards extrinsic signals...
In vivo analysis of retroviral enhancer mutations in hematopoietic cells: SP1/EGR1 and ETS/GATA motifs contribute to long terminal repeat specificityAnke Wahlers
Department of Cell and Virus Genetics, Heinrich Pette Institute, D 20251 Hamburg, Germany
J Virol 76:303-12. 2002....
Clonal dominance of hematopoietic stem cells triggered by retroviral gene markingOlga Kustikova
Bone Marrow Transplantation, University Hospital Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany
Science 308:1171-4. 2005..Transcriptional dysregulation occurred in all 12 insertion sites analyzed. These findings have major implications for diagnostic gene marking and the discovery of genes regulating stem cell turnover...
Simplified generation of high-titer retrovirus producer cells for clinically relevant retroviral vectors by reversible inclusion of a lox-P-flanked marker geneRainer Loew
EUFETS AG, Vollmersbachstrasse 66, D 55743 Idar Oberstein, Germany
Mol Ther 9:738-46. 2004..The single lox-P site retained in the vector backbone does not affect gene expression level or fidelity of RNA processing...
Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cellsMichael D Milsom
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
Cancer Res 68:6171-80. 2008..These studies have direct translational relevance to ongoing clinical gene therapy studies using MGMT(P140K), whereas the novel mechanistic findings are relevant to the basic understanding of DNA repair by MGMT...
Down-regulation of retroviral transgene expression during differentiation of progenitor-derived dendritic cellsCarsten Lindemann
EUFETS AG, Idar-Oberstein, Germany
Exp Hematol 30:150-7. 2002..An improvement of retroviral vectors mediating stable transgenic expression is necessary for therapeutic approaches using gene-modified dendritic cells...
Lenti in red: progress in gene therapy for human hemoglobinopathiesChristof von Kalle
Division of Expermental Hematology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
J Clin Invest 114:889-91. 2004..While some safety concerns must be addressed, this study is an important step toward potential clinical trials of gene therapy for hemoglobinopathies...
Multidrug resistance 1 gene transfer can confer chemoprotection to human peripheral blood progenitor cells engrafted in immunodeficient miceBernd Schiedlmeier
German Cancer Research Center, 69120 Heidelberg, Germany
Hum Gene Ther 13:233-42. 2002..This is the first report showing that cytostatic drug resistance gene therapy can mediate chemoprotection of human clinically relevant stem cell populations with marrow engraftment potential...
Engineered long terminal repeats of retroviral vectors enhance transgene expression in hepatocytes in vitro and in vivoKanji Yamaguchi
Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, 606 8507, Kyoto, Japan
Mol Ther 8:796-803. 2003..5- to 5-fold in comparison with a Moloney murine leukemia virus-based vector or a vector containing the wild-type LTR of SFFVp, respectively, in murine hepatocytes in vivo...
Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiencySusannah I Thornhill
Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
Mol Ther 16:590-8. 2008....
Retroviral vectors for high-level transgene expression in T lymphocytesBoris Engels
, Robert-Rossle-Strasse 10, 13092 Berlin, Germany
Hum Gene Ther 14:1155-68. 2003..In summary, MP71 vectors are useful tools for stable, high-level gene expression in T lymphocytes, for example, in the expression of T cell receptor genes...
HOXB4 enforces equivalent fates of ES-cell-derived and adult hematopoietic cellsSandra Pilat
Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohr Gasse 7, 1030 Vienna, Austria
Proc Natl Acad Sci U S A 102:12101-6. 2005..Provided that HOXB4 levels are kept within a certain therapeutic window, ES cells also carry the potential of efficient and safe somatic gene therapy...
In vivo selection of transduced hematopoietic stem cells and little evidence of their conversion into hepatocytes in vivoKanji Yamaguchi
Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto, Japan
J Hepatol 45:681-7. 2006..CONCLUSIONS: This vector expressed a drug-resistance gene in HSCs highly enough to protect them from the drugs. But, the conversion of HSCs into hepatocytes in vivo might be a rare event in this model...
Medicine. Gene therapy--new challenges aheadDavid A Williams
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
Science 302:400-1. 2003..reinforces the need to develop even more specific gene therapy interventions...
Overexpression of MDR1 using a retroviral vector differentially regulates genes involved in detoxification and apoptosis and confers radioprotectionPatrick Maier
Department of Radiation Oncology, Mannheim Medical Centre, University of Heidelberg, 68167 Mannheim, Germany
Radiat Res 166:463-73. 2006..These results have important implications for understanding the mechanisms by which MDR1 gene therapy can protect normal tissues from radiation- or chemotherapy-induced damage during tumor treatment...
Dose finding with retroviral vectors: correlation of retroviral vector copy numbers in single cells with gene transfer efficiency in a cell populationOlga S Kustikova
Department of Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, D-20251 Hamburg, Germany
Blood 102:3934-7. 2003..Therefore, limiting retroviral gene transfer to approximately 30% may be suggested to avoid generating clones containing multiple insertions...
MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AMLMichael Heuser
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
Blood 110:1639-47. 2007..MN1 is a unique oncogene in hematopoiesis that both promotes proliferation/self-renewal and blocks differentiation, and may become useful as a predictive marker in AML treatment...
CD34 modulates the trafficking behavior of hematopoietic cells in vivoClaudia Lange
Bone Marrow Transplantation, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany
Stem Cells Dev 16:297-304. 2007..Our data indicate that CD34 expression in mature blood cells has a suppressive effect on cellular trafficking to hematopoietic stroma organs, thereby supporting a modulating role of the CD34 molecule in cytoadhesion...
High-level ectopic HOXB4 expression confers a profound in vivo competitive growth advantage on human cord blood CD34+ cells, but impairs lymphomyeloid differentiationBernhard Schiedlmeier
Heinrich Pette Institute, Department of Cell and Virus Genetics, Hamburg, Germany
Blood 101:1759-68. 2003..01). These results show for the first time unwanted side effects of ectopic HOXB4 expression and therefore underscore the need to carefully determine the therapeutic window of HOXB4 expression levels before initializing clinical trials...
What are the consequences of the fourth case?Christopher Baum
Mol Ther 15:1401-2. 2007
Upstream conserved sequences of mouse leukemia viruses are important for high transgene expression in lymphoid and hematopoietic cellsAnke Wahlers
Heinrich-Pette-Institute, Department of Cell and Virus Genetics, 20251 Hamburg, Germany
Mol Ther 6:313-20. 2002..These results provide novel clues for the manipulation of retrovirus replication and vector tropism...
Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trialsElke Will
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
Mol Ther 15:782-91. 2007....
Tumor cells escape suicide gene therapy by genetic and epigenetic instabilityOliver Frank
Department of Cell and Virus Genetics, Heinrich-Pette-Institute, Hamburg, Germany
Blood 104:3543-9. 2004..Considering the mechanisms of escape identified here, the proactive use of suicide genes to prevent complications of insertional mutagenesis may still be efficient...
Retroviral pseudotransduction for targeted cell manipulationMelanie Galla
Division of Experimental Hematology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA
Mol Cell 16:309-15. 2004..Thus, retrovirally delivered mRNA may serve as an immediate translation template if not being reverse transcribed. This approach allows multiple modifications for targeted and reversible cell manipulation with nucleic acids...
Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virusJan van Lunzen
Infectious Diseases Unit, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Mol Ther 15:1024-33. 2007..In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus...
Role of the Multidrug Resistance Protein 1 in protection from heavy metal oxyanions: investigations in vitro and in MRP1-deficient miceAurelio Lorico
Department of Tumor Biology, Norwegian Radium Hospital, Montebello, 0310, Norway
Biochem Biophys Res Commun 291:617-22. 2002..p. with sodium arsenite. It is conceivable that, in vivo, other pump(s) effectively vicariate for MRP1-mediated transport of heavy metal oxyanions...
Gamma-glutamylcysteine synthetase and L-buthionine-(S,R)-sulfoximine: a new selection strategy for gene-transduced neural and hematopoietic stem/progenitor cellsAurelio Lorico
Department of Tumor Biology, Norwegian Radium Hospital, Montebello, Oslo 0310, Norway
Hum Gene Ther 16:711-24. 2005..These results provide proof of principle that somatic stem/progenitor cells, transduced simultaneously with a potentially curative gene and gamma-GCSh, can be selected by treatment with BSO before in vivo transplantation...
Gene therapy needs both trials and new strategiesDavid Williams
Nature 429:129. 2004
Unmodified Cre recombinase crosses the membraneElke Will
Department of Cell and Virus Genetics, Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse 52, D-20251 Hamburg, Germany
Nucleic Acids Res 30:e59. 2002..We conclude that Cre enyzme itself or its intrinsic membrane-permeating moiety are attractive tools for direct manipulation of mammalian cells...
