Manuela Germeshausen

Summary

Affiliation: Hannover Medical School
Country: Germany

Publications

  1. ncbi request reprint [Congenital amegakaryocytic thrombocytopenia (CAMT) - a defect of the thrombopoietin receptor c-Mpl]
    M Germeshausen
    Abt Pädiatrische Hämatologie und Onkologie, Medizinische Hochschule Hannover, Germany
    Klin Padiatr 213:155-61. 2001
  2. doi request reprint The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Hum Mutat 34:905-14. 2013
  3. doi request reprint In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Blood 113:668-70. 2009
  4. pmc Digenic mutations in severe congenital neutropenia
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology Molecular Hematopoiesis, Medizinische Hochschule Hannover, Carl Neuberg Str 1, D 30625 Hannover, Germany
    Haematologica 95:1207-10. 2010
  5. ncbi request reprint Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: Results of a long-term survey
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany
    Blood 109:93-9. 2007
  6. ncbi request reprint An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia
    M Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany
    Leukemia 19:611-7. 2005
  7. ncbi request reprint MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Hum Mutat 27:296. 2006
  8. ncbi request reprint Implications of mutations in hematopoietic growth factor receptor genes in congenital cytopenias
    M Germeshausen
    Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
    Ann N Y Acad Sci 938:305-20; discussion 320-1. 2001
  9. 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
  10. doi request reprint 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

Publications29

  1. ncbi request reprint [Congenital amegakaryocytic thrombocytopenia (CAMT) - a defect of the thrombopoietin receptor c-Mpl]
    M Germeshausen
    Abt Pädiatrische Hämatologie und Onkologie, Medizinische Hochschule Hannover, Germany
    Klin Padiatr 213:155-61. 2001
    ..TPO is not only involved in the regulation of megakaryocytopoiesis but also in early hematopoiesis. This seems to be the reason for the general defect in hematopoiesis in CAMT leading to the development of pancytopenia...
  2. doi request reprint The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Hum Mutat 34:905-14. 2013
    ..Specific ELANE mutations have limited predictive value for leukemogenesis; the risk for leukemia was correlated with disease severity rather than with occurrence of an ELANE mutation...
  3. doi request reprint In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Blood 113:668-70. 2009
    ....
  4. pmc Digenic mutations in severe congenital neutropenia
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology Molecular Hematopoiesis, Medizinische Hochschule Hannover, Carl Neuberg Str 1, D 30625 Hannover, Germany
    Haematologica 95:1207-10. 2010
    ..Our results suggest that digenicity may underlie this disorder of myelopoiesis at least in some congenital neutropenia patients...
  5. ncbi request reprint Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: Results of a long-term survey
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany
    Blood 109:93-9. 2007
    ..Our results strongly suggest that acquisition of a CSF3R mutation is an early event in leukemogenesis that has to be accompanied by cooperating molecular events, which remain to be defined...
  6. ncbi request reprint An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia
    M Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany
    Leukemia 19:611-7. 2005
    ..Our results provide direct evidence for the in vivo expression of a truncated G-CSFR in leukemic cells, which emerged in the absence of rh-G-CSF treatment and transduces proliferative signals...
  7. ncbi request reprint MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Hum Mutat 27:296. 2006
    ..Using in vitro assays with hematopoietic progenitors from patients of both patient groups we could provide experimental evidence for a residual activity of the thrombopoietin receptor in CAMT II patients...
  8. ncbi request reprint Implications of mutations in hematopoietic growth factor receptor genes in congenital cytopenias
    M Germeshausen
    Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
    Ann N Y Acad Sci 938:305-20; discussion 320-1. 2001
    ..In contrast, mutations in the G-CSF receptor in CN are acquired and are most probably connected with progression of the neutropenia into MDS/leukemia as a result of a loss of differentiation signaling...
  9. 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...
  10. doi request reprint 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. doi request reprint Advances in the understanding of congenital amegakaryocytic thrombocytopenia
    Matthias Ballmaier
    Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
    Br J Haematol 146:3-16. 2009
    ..The essential roles of thrombopoietin as a lineage specific regulator of platelet production and as a regulator of haematopoietic stem cell function are reflected in the haematological defects seen in affected individuals...
  12. doi request reprint G-CSF receptor mutations in patients with congenital neutropenia
    Manuela Germeshausen
    Department of Pediatric Hematology Oncology, Medical University Hannover, Hannover, Germany
    Curr Opin Hematol 15:332-7. 2008
    ..Congenital neutropenia is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10/l...
  13. doi request reprint 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...
  14. ncbi request reprint Thrombopoietin is essential for the maintenance of normal hematopoiesis in humans: development of aplastic anemia in patients with congenital amegakaryocytic thrombocytopenia
    M Ballmaier
    Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, D 30625 Hannover, Germany
    Ann N Y Acad Sci 996:17-25. 2003
    ..On the other hand, the incidence of development of aplastic anemia in CAMT is not clear owing to difficult and not consistent diagnosis of this disease...
  15. doi request reprint Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene
    El Harith Abdelghaffar El-Harith
    Institute of Human Genetics, Medical University of Hannover, Hannover, Germany
    Br J Haematol 144:185-94. 2009
    ..In the families described the mode of inheritance could be regarded as autosomal-recessive with possible mild heterozygote manifestation rather than autosomal-dominant with high penetrance as usually seen in FT...
  16. doi request reprint Granulocyte colony-stimulating factor (G-CSF) treatment of childhood acute myeloid leukemias that overexpress the differentiation-defective G-CSF receptor isoform IV is associated with a higher incidence of relapse
    Stephanie Ehlers
    Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany
    J Clin Oncol 28:2591-7. 2010
    ..However, a trend toward an increased incidence of relapses in the standard-risk (SR) group after G-CSF treatment was observed...
  17. ncbi request reprint 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...
  18. ncbi request reprint Severe congenital neutropenia: inheritance and pathophysiology
    Julia Skokowa
    Department of Pediatric Hematology Oncology, Medical University Hannover, Hannover, Germany
    Curr Opin Hematol 14:22-8. 2007
    ..5 x 10/l. In this review we summarize our current knowledge on inheritance and pathophysiolgy of congenital neutropenia...
  19. doi request reprint Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment
    Matthias Ballmaier
    Department of Pediatric Hematology and Oncology Molecular Hematopoiesis, Hannover Medical School, Hannover, Germany
    Semin Thromb Hemost 37:673-81. 2011
    ..The present review summarizes clinical and laboratory data for 96 patients with CAMT, reported since 1990...
  20. ncbi request reprint 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...
  21. ncbi request reprint LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia
    Julia 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...
  22. ncbi request reprint c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia
    M Ballmaier
    Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Germany
    Blood 97:139-46. 2001
    ..The type of mutations correlated with the clinical course of the disease. We propose a defective c-Mpl expression due to c-mpl mutations as the cause for thrombocytopenia and progression into pancytopenia seen in patients with CAMT...
  23. ncbi request reprint Congenital amegakaryocytic thrombocytopenia: a retrospective clinical analysis of 20 patients
    Stephanie King
    Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
    Br J Haematol 131:636-44. 2005
    ..Fifteen patients were treated with haematopoietic stem cell transplantation, four of whom died of transplantation-related events...
  24. ncbi request reprint Mutations in neutrophil elastase causing congenital neutropenia lead to cytoplasmic protein accumulation and induction of the unfolded protein response
    Inga Köllner
    Institute of Cell and Molecular Pathology, The Institute of Virology, the Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany
    Blood 108:493-500. 2006
    ....
  25. ncbi request reprint Thrombopoietin induces the generation of distinct Stat1, Stat3, Stat5a and Stat5b homo- and heterodimeric complexes with different kinetics in human platelets
    H Schulze
    Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany
    Exp Hematol 28:294-304. 2000
    ..Our aim was to elucidate which Stat-complexes are formed in TPO signal transduction in human blood platelets...
  26. ncbi request reprint Mutations in the gene encoding neutrophil elastase (ELA2) are not sufficient to cause the phenotype of congenital neutropenia
    M Germeshausen
    Department of Paediatric Haematology and Oncology, Medizinische Hochschule Hannover, Germany
    Br J Haematol 115:222-4. 2001
    ..We conclude that ELA2 mutations are not the single cause of CN although they might be a necessary prerequisite for the expression of the neutropenic phenotype in a subgroup of CN patients...
  27. ncbi request reprint Congenital dysgranulopoietic neutropenia
    Lale Olcay
    Unit of Pediatric Hematology, Ankara Oncology Hospital, Demetevler, Ankara, Turkiye
    Pediatr Blood Cancer 50:115-9. 2008
    ..The daughter's karyotype revealed 46,XX/46,XX, t(1;8). No ELA2 or G-CSFR mutation was detected. These findings support stem cell involvement in CDN...
  28. ncbi request reprint The clinical, immunohematological, and molecular study of Iranian patients with severe congenital neutropenia
    Nima Rezaei
    Immunology, Asthma and Allergy Research Institute, Department of Allergy and Clinical Immunology of Children Medical Center, Medical Sciences University of Tehran, Tehran 14194, Iran
    J Clin Immunol 27:525-33. 2007
    ..Three patients died because of a severe infection. Although SCN is a rare disorder, early onset of severe and recurrent infections should always raise a suspicion, which deserves further evaluation for detecting such disorder...
  29. ncbi request reprint Reduced intensity hematopoietic stem-cell transplantation across human leukocyte antigen barriers in a patient with congenital amegakaryocytic thrombocytopenia and monosomy 7
    Macgregor Steele
    Marrow Failure and Myelodysplasia Programme, and Blood and Marrow Transplantation Section, Division of Haematology and Oncology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada
    Pediatr Blood Cancer 45:212-6. 2005
    ..Thus, reduced intensity conditioning might be a feasible approach to stem-cell transplantation in patients with CAMT who do not have a related donor and who are at increased risk of toxicity from standard conditioning regimens...