Christoph Klein

Summary

Affiliation: Hannover Medical School
Country: Germany

Publications

  1. ncbi Severe congenital neutropenia: new genes explain an old disease
    Georg Bohn
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Curr Opin Rheumatol 19:644-50. 2007
  2. pmc Prevalence, phenotype and inheritance of benign neutropenia in Arabs
    Srdjan Denic
    Department of Internal Medicine, Faculty of Medicine and Health Sciences, UAE University, Al Ain, UAE
    BMC Blood Disord 9:3. 2009
  3. doi Genetic defects in severe congenital neutropenia: emerging insights into life and death of human neutrophil granulocytes
    Christoph Klein
    Department of Pediatric Hematology Oncology, Hannover Medical School, Germany
    Annu Rev Immunol 29:399-413. 2011
  4. ncbi HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)
    Christoph Klein
    Department of Pediatric Hematology Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Genet 39:86-92. 2007
  5. ncbi Genetic insights into congenital neutropenia
    Christoph Klein
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    Clin Rev Allergy Immunol 38:68-74. 2010
  6. pmc The phenotype of human STK4 deficiency
    Hengameh Abdollahpour
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    Blood 119:3450-7. 2012
  7. ncbi Transcription factor Gfi1 restricts B cell-mediated autoimmunity
    Chozhavendan Rathinam
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    J Immunol 181:6222-9. 2008
  8. pmc A syndrome with congenital neutropenia and mutations in G6PC3
    Kaan Boztug
    Hannover Medical School, Hannover, Germany
    N Engl J Med 360:32-43. 2009
  9. pmc Transcriptional repressor Gfi1 integrates cytokine-receptor signals controlling B-cell differentiation
    Chozhavendan Rathinam
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    PLoS ONE 2:e306. 2007
  10. doi Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Blood 111:4954-7. 2008

Detail Information

Publications42

  1. ncbi Severe congenital neutropenia: new genes explain an old disease
    Georg Bohn
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Curr Opin Rheumatol 19:644-50. 2007
    ..This review summarizes the recent advances in the diagnosis and molecular characterization of isolated and syndromal forms of severe congenital neutropenia...
  2. pmc Prevalence, phenotype and inheritance of benign neutropenia in Arabs
    Srdjan Denic
    Department of Internal Medicine, Faculty of Medicine and Health Sciences, UAE University, Al Ain, UAE
    BMC Blood Disord 9:3. 2009
    ..CONCLUSION: Arabs have a high prevalence of benign neutropenia that may be inherited as an autosomal dominant trait...
  3. doi Genetic defects in severe congenital neutropenia: emerging insights into life and death of human neutrophil granulocytes
    Christoph Klein
    Department of Pediatric Hematology Oncology, Hannover Medical School, Germany
    Annu Rev Immunol 29:399-413. 2011
    ..This unexpected diversity of factors suggests that multiple pathways are involved in the pathogenesis of congenital neutropenia...
  4. ncbi HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)
    Christoph Klein
    Department of Pediatric Hematology Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Genet 39:86-92. 2007
    ..Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development...
  5. ncbi Genetic insights into congenital neutropenia
    Christoph Klein
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    Clin Rev Allergy Immunol 38:68-74. 2010
    ..g. p14-deficiency or G6PC3-deficiency. The clinical and genetic findings of various neutropenia syndromes are being discussed...
  6. pmc The phenotype of human STK4 deficiency
    Hengameh Abdollahpour
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    Blood 119:3450-7. 2012
    ..STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome...
  7. ncbi Transcription factor Gfi1 restricts B cell-mediated autoimmunity
    Chozhavendan Rathinam
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    J Immunol 181:6222-9. 2008
    ..Dysregulation of multiple transcription factors and cell cycle control elements may contribute to B cell-dependent autoimmunity. Gfi1 thus emerges as a novel master regulator restricting autoimmunity...
  8. pmc A syndrome with congenital neutropenia and mutations in G6PC3
    Kaan Boztug
    Hannover Medical School, Hannover, Germany
    N Engl J Med 360:32-43. 2009
    ..In many patients, the genetic causes of severe congenital neutropenia are unknown...
  9. pmc Transcriptional repressor Gfi1 integrates cytokine-receptor signals controlling B-cell differentiation
    Chozhavendan Rathinam
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    PLoS ONE 2:e306. 2007
    ..Thus, Gfi1 selectively specifies IL7-dependent development of B cells from CLP1 progenitors, providing clues to the transcriptional networks integrating cytokine signals and lymphoid differentiation...
  10. doi Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Blood 111:4954-7. 2008
    ..Therefore, our findings suggest that HAX1 isoforms may play a distinctive role in the neuronal system...
  11. pmc HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI
    Kaan Boztug
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    Am J Med Genet A 152:3157-63. 2010
    ..This study provides first in vivo evidence of aberrant neuroimaging findings associated with HAX1 deficiency in SCN patients...
  12. ncbi Novel genetic etiologies of severe congenital neutropenia
    Kaan Boztug
    Department of Pediatric Hematology Oncology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Curr Opin Immunol 21:472-80. 2009
    ..Despite our increasing knowledge of the genetic etiologies of SCN, the molecular pathophysiology underlying these disorders remains only partially understood...
  13. doi Establishment of immortalized multipotent hematopoietic progenitor cell lines by retroviral-mediated gene transfer of beta-catenin
    Christian Templin
    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
    Exp Hematol 36:204-15. 2008
    ..In the present study, we show that beta-catenin plays an essential role in the immortalization of hematopoietic progenitor cells (HPCs)...
  14. pmc A complex immunodeficiency is based on U1 snRNP-mediated poly(A) site suppression
    Jörg Langemeier
    Cell and Virus Genetics Group, Institute for Virology, Hannover Medical School, Hannover, Germany
    EMBO J 31:4035-44. 2012
    ..Moreover, our data endorse the recently described role of U1 snRNP in suppression of intronic poly(A) sites, which is here deleterious for p14 mRNA biogenesis...
  15. doi Risk factors and prognosis in T-cell posttransplantation lymphoproliferative diseases: reevaluation of 163 cases
    Christina Tiede
    Institute of Pathology, Hannover Medical School, Hannover, Germany
    Transplantation 95:479-88. 2013
    ..Therefore, we aimed to provide an overview and a retrospective analysis of this rare PTLD subtype...
  16. doi Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy
    Daniel Kotlarz
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Gastroenterology 143:347-55. 2012
    ..We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder...
  17. doi Development of novel efficient SIN vectors with improved safety features for Wiskott-Aldrich syndrome stem cell based gene therapy
    Inés Avedillo Díez
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    Mol Pharm 8:1525-37. 2011
    ..Therefore, the described SIN vectors appear to be good candidates for potential use in a safer new gene therapy protocol for WAS, with decreased risk of insertional mutagenesis...
  18. doi Genetic etiologies of severe congenital neutropenia
    Kaan Boztug
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    Curr Opin Pediatr 23:21-6. 2011
    ..To review recent advances in severe congenital neutropenia (SCN) syndromes...
  19. doi Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia
    Cornelia Zeidler
    Department of Paediatric Haematology Oncology, Medical University Hannover, Hannover, Germany
    Br J Haematol 144:459-67. 2009
    ..As the majority of patients benefit from G-CSF administration, HSCT should be restricted to non-responders and patients with leukaemic transformation...
  20. doi EBV-specific T-cell immunity in pediatric solid organ graft recipients with posttransplantation lymphoproliferative disease
    Nadine Wilsdorf
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Transplantation 95:247-55. 2013
    ..We present data on EBV-specific T cells in children treated with rituximab with or without chemotherapy on the pediatric PTLD Pilot 2005 protocol...
  21. doi Congenital neutropenia syndromes
    Kaan Boztug
    Department of Pediatric Hematology Oncology, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Immunol Allergy Clin North Am 28:259-75, vii-viii. 2008
    ..Recently, several novel genetic defects were described in patients with congenital neutropenia, shedding light on the pathophysiology of these rare diseases...
  22. pmc MAPKAP kinase MK2 maintains self-renewal capacity of haematopoietic stem cells
    Jessica Schwermann
    Institute of Biochemistry, Hannover Medical School, Hannover, Germany
    EMBO J 28:1392-406. 2009
    ..Thus, MK2 emerges as a regulator of HSC homeostasis, which could act through chromatin remodelling by the PcG complex...
  23. ncbi Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment
    Zhenyu Ju
    Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, 30625 Hannover, Germany
    Nat Med 13:742-7. 2007
    ..Taken together, these results show that telomere dysfunction induces alterations of the environment that can have implications for organismal aging and cell transplantation therapies...
  24. ncbi High-content cytometry and transcriptomic biomarker profiling of human B-cell activation
    Christian Hennig
    Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany Electronic address
    J Allergy Clin Immunol 133:172-80.e1-10. 2014
    ..Primary antibody deficiencies represent the most prevalent, although very heterogeneous, group of inborn immunodeficiencies, with a puzzling complexity of cellular and molecular processes involved in disease pathogenesis...
  25. doi Characteristics of early and late PTLD development in pediatric solid organ transplant recipients
    Tilmann Schober
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    Transplantation 95:240-6. 2013
    ..The purpose of this study was to identify the factors associated with the development of early- and late-onset PTLD in pediatric solid organ transplant recipients...
  26. pmc PD-L1 blockade effectively restores strong graft-versus-leukemia effects without graft-versus-host disease after delayed adoptive transfer of T-cell receptor gene-engineered allogeneic CD8+ T cells
    Wolfgang Koestner
    Department of Pediatric Hematology Oncology and Blood Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
    Blood 117:1030-41. 2011
    ..These data suggest a clinical approach in which the AT of gene-modified allogeneic T cells early after transplantation can provide a potent GVL effect without GVHD, whereas later AT is effective only with concurrent PD-L1 blockade...
  27. pmc Stem-cell gene therapy for the Wiskott-Aldrich syndrome
    Kaan Boztug
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    N Engl J Med 363:1918-27. 2010
    ..Funded by Deutsche Forschungsgemeinschaft and others; German Clinical Trials Register number, DRKS00000330.)...
  28. doi Lethal graft-versus-host disease in congenital neutropenia caused by p14 deficiency after allogeneic bone marrow transplantation from an HLA-identical sibling
    Georg Bohn
    Department of Pediatric Hematology and Oncology, Hannover Medical School, OE 6780, Carl Neuberg Str 1, 30625 Hannover, Germany
    Pediatr Blood Cancer 51:436-8. 2008
    ..We hypothesize that p14 deficiency predisposes to GvHD through increased TNF-alpha production. Adequate genetic testing is needed to prospectively assess potential risk factors for GvHD in defined SCN subgroups...
  29. ncbi CNS or bone marrow involvement as risk factors for poor survival in post-transplantation lymphoproliferative disorders in children after solid organ transplantation
    Britta Maecker
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    J Clin Oncol 25:4902-8. 2007
    ..To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation...
  30. ncbi The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell development and function
    Chozhavendan Rathinam
    Department of Pediatric Hematology Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Immunity 22:717-28. 2005
    ..In conclusion, we have identified Gfi1 as a critical transcription factor that controls DC versus macrophage development and dissociates DC maturation and activation...
  31. ncbi Large granular lymphocyte proliferation and revertant mosaicism: two rare events in a Wiskott-Aldrich syndrome patient
    Kaan Boztug
    Department of Pediatric Hematology Oncology, Medical School Hannover, D 30625 Hannover, Germany
    Haematologica 92:e43-5. 2007
    ..Our report points to diagnostic difficulties in the presence of partial WASP reversions and LGL...
  32. pmc Modified Lentiviral LTRs Allow Flp Recombinase-mediated Cassette Exchange and In Vivo Tracing of "Factor-free" Induced Pluripotent Stem Cells
    Johannes Kuehle
    Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Mol Ther 22:919-28. 2014
    ..These findings support the concept of creating clonotypically defined exchangeable and traceable pluripotent stem cells for disease research and cell therapy. ..
  33. ncbi Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome
    Kaan Boztug
    Department of Pediatric Hematology Oncology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Curr Opin Mol Ther 8:390-5. 2006
    ..The first clinical trial is currently being conducted to assess the feasibility, toxicity, and potential therapeutic benefit of transplanting autologous WASP-reconstituted hematopoietic stem cells...
  34. pmc Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome
    Daniel Kotlarz
    Department of Pediatric Hematology Oncology, Hannover Medical School, 30625 Hannover, Germany
    J Exp Med 210:433-43. 2013
    ..Our study indicates that human IL-21R deficiency causes an immunodeficiency and highlights the need for early diagnosis and allogeneic hematopoietic stem cell transplantation in affected children...
  35. doi The role of laparoscopic techniques in children with suspected post-transplantation lymphoproliferative disorders
    Martin L Metzelder
    Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
    J Laparoendosc Adv Surg Tech A 21:767-70. 2011
    ..To assess the role of minimally invasive surgery (MIS) to diagnose post-transplantation lymphoproliferative disorder (PTLD) in pediatric patients...
  36. ncbi Retroviral WASP gene transfer into human hematopoietic stem cells reconstitutes the actin cytoskeleton in myeloid progeny cells differentiated in vitro
    Ricardo A Dewey
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Exp Hematol 34:1161-9. 2006
    ..Compared with the conventional treatment using allogeneic bone marrow transplantation, hematopoietic stem cell gene therapy might offer more specific and less toxic therapeutic options...
  37. doi Prolonged isolated red blood cell transfusion requirement after allogeneic blood stem cell transplantation: identification of patients at risk
    Daphne Dahl
    Departments of Pediatric Hematology Oncology, Medizinische Hochschule Hannover, Hannover, Germany
    Transfusion 50:649-55. 2010
    ..The clinical variable "prolonged isolated red blood cell transfusion requirement" (PRTR) was evaluated as a trigger for an extended diagnostic workup...
  38. doi Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 deficiency: novel genotypes and phenotypic variability in severe congenital neutropenia
    Kaan Boztug
    Research Center for Molecular Medicine of the Austrian Academy of Sciences CeMM, Vienna, Austria
    J Pediatr 160:679-683.e2. 2012
    ..To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3)...
  39. doi Pain reduction in children during port-à-cath catheter puncture using local anaesthesia with EMLA™
    Birke Lüllmann
    Department of Paediatric Haematology and Oncology, Medical University, Hannover, Germany
    Eur J Pediatr 169:1465-9. 2010
    ..Alleviating pain is of high importance for children undergoing chemotherapy. Eutectic mixture of lidocain-prilocain cream (EMLA) is assumed to require 60 min application time...
  40. ncbi Cytogenetic characterization of a BCR-ABL transduced mouse cell line
    Cornelia Rudolph
    Institute of Cell and Molecular Pathology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Cancer Genet Cytogenet 161:51-6. 2005
    ....
  41. ncbi Reevaluation of bone marrow-derived cells as a source for hepatocyte regeneration
    Tobias Cantz
    Laboratory of Cell and Gene Therapy, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
    Cell Transplant 13:659-66. 2004
    ..Thus, potential therapeutic prospects of hematopoietic stem cell therapy for liver disease have to be critically reassessed...
  42. ncbi Gene therapy for inherited disorders of haematopoietic cells
    Christoph Klein
    Experimental Hematology and Oncology, Department of Pediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
    Hematol J 5:103-11. 2004
    ....