W Kern

Summary

Affiliation: University of Munich
Country: Germany

Publications

  1. ncbi [Quantification of minimal residual disease by multiparameter flow cytometry in acute myeloid leukemia. From diagnosis to prognosis]
    Wolfgang Kern
    Labor für Leukämiediagnostik, Klinikum der Universitat Munchen Grosshadern, 81366 München
    Med Klin (Munich) 100:54-9. 2005
  2. ncbi [Immunophenotyping in modern leukemia diagnosis]
    W Kern
    Labor für Leukämiediagnostik, Medizinische Klinik III, Klinikum der Universitat Munchen Grosshadern
    Dtsch Med Wochenschr 130:215-9. 2005
  3. ncbi Detection of t(14;18)(q32;q21) in B-cell chronic lymphocytic leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Muenchen, Germany
    Arch Pathol Lab Med 129:410-1. 2005
  4. ncbi Gene expression profiling as a diagnostic tool in acute myeloid leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Munich, Germany
    Am J Pharmacogenomics 4:225-37. 2004
  5. ncbi Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Ludwig Maximilians University, University Hospital Grosshadern, Department of Internal Medicine III, 81366 Muenchen, Germany
    Blood 104:3078-85. 2004
  6. ncbi New insights into MLL gene rearranged acute leukemias using gene expression profiling: shared pathways, lineage commitment, and partner genes
    A Kohlmann
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig Maximilians University, 81377 Munich, Germany
    Leukemia 19:953-64. 2005
  7. ncbi Successful modulation of high-dose cytosine arabinoside metabolism in acute myeloid leukaemia by haematopoietic growth factors: no effect of ribonucleotide reductase inhibitors fludarabine and gemcitabine
    J Braess
    Medical Clinic III, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
    Br J Haematol 109:388-95. 2000
  8. ncbi Hepatic arterial infusion with oxaliplatin, folinic acid, and 5-fluorouracil in patients with hepatic metastases from colorectal cancer: role of carcino-embryonic antigen in assessment of response
    W Kern
    University Hospital Grosshadern, Department of Medicine III, Ludwig Maximilians University, 81366 München, Germany
    Anticancer Res 20:4973-5. 2000
  9. doi AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features
    T Haferlach
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 23:934-43. 2009
  10. ncbi Detailed analysis of FLT3 expression levels in acute myeloid leukemia
    Florian Kuchenbauer
    Department of Internal Medicine III, Ludwig Maximilians University of Munich, University Hospital Grosshadern, Munich, Germany
    Haematologica 90:1617-25. 2005

Collaborators

Detail Information

Publications121 found, 100 shown here

  1. ncbi [Quantification of minimal residual disease by multiparameter flow cytometry in acute myeloid leukemia. From diagnosis to prognosis]
    Wolfgang Kern
    Labor für Leukämiediagnostik, Klinikum der Universitat Munchen Grosshadern, 81366 München
    Med Klin (Munich) 100:54-9. 2005
    ..Due to its close correlation with the course of the disease and with the risk of relapse the MRD represents an important prognostic parameter which is increasingly used for stratification of therapy in clinical trials...
  2. ncbi [Immunophenotyping in modern leukemia diagnosis]
    W Kern
    Labor für Leukämiediagnostik, Medizinische Klinik III, Klinikum der Universitat Munchen Grosshadern
    Dtsch Med Wochenschr 130:215-9. 2005
  3. ncbi Detection of t(14;18)(q32;q21) in B-cell chronic lymphocytic leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Muenchen, Germany
    Arch Pathol Lab Med 129:410-1. 2005
    ..Therapy is highly diverse between both diseases. We describe a case with cytomorphologically and immunologically proven B-cell chronic lymphocytic leukemia in which t(14;18)(q32;q21) was found...
  4. ncbi Gene expression profiling as a diagnostic tool in acute myeloid leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Munich, Germany
    Am J Pharmacogenomics 4:225-37. 2004
    ..Furthermore, gene expression profiling may also lead to the detection of new biologically defined and clinically relevant subtypes in leukemia and guide therapeutic decision-making in the future...
  5. ncbi Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Ludwig Maximilians University, University Hospital Grosshadern, Department of Internal Medicine III, 81366 Muenchen, Germany
    Blood 104:3078-85. 2004
    ..MFC-based quantification of MRD reveals important prognostic information in unselected patients with AML in addition to cytogenetics and should be further evaluated and used in clinical trials...
  6. ncbi New insights into MLL gene rearranged acute leukemias using gene expression profiling: shared pathways, lineage commitment, and partner genes
    A Kohlmann
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig Maximilians University, 81377 Munich, Germany
    Leukemia 19:953-64. 2005
    ..Taken together, the identified molecular expression pattern of MLL fusion gene samples and biological networks revealed new insights into the aberrant transcriptional program in 11q23/MLL leukemias...
  7. ncbi Successful modulation of high-dose cytosine arabinoside metabolism in acute myeloid leukaemia by haematopoietic growth factors: no effect of ribonucleotide reductase inhibitors fludarabine and gemcitabine
    J Braess
    Medical Clinic III, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
    Br J Haematol 109:388-95. 2000
    ..8 pmol/min/mg protein) to 34.3 pmol/min/mg protein at 24 h (1.15-fold increase) and 54.5 pmol/min/mg protein at 48 h (1. 83-fold increase). The raise in dCK activity over 48 h was significant (P < 0.013)...
  8. ncbi Hepatic arterial infusion with oxaliplatin, folinic acid, and 5-fluorouracil in patients with hepatic metastases from colorectal cancer: role of carcino-embryonic antigen in assessment of response
    W Kern
    University Hospital Grosshadern, Department of Medicine III, Ludwig Maximilians University, 81366 München, Germany
    Anticancer Res 20:4973-5. 2000
    ..Therapy for patients with hepatic metastases from colorectal cancer (CRC) remains controversial and may be improved by regional oxaliplatin which proved to be effective when administered systemically to patients with advanced CRC...
  9. doi AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features
    T Haferlach
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 23:934-43. 2009
    ..In conclusion, AML with t(8;16) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features and is a specific subtype of AML...
  10. ncbi Detailed analysis of FLT3 expression levels in acute myeloid leukemia
    Florian Kuchenbauer
    Department of Internal Medicine III, Ludwig Maximilians University of Munich, University Hospital Grosshadern, Munich, Germany
    Haematologica 90:1617-25. 2005
    ..Although new FLT3 mutations are being increasing by investigated, the role of FLT3 expression levels in wild type as well as in mutated FLT3 has only been infrequently addressed...
  11. ncbi The pharmacodynamic basis for the increased antileukaemic efficacy of cytosine arabinoside-based treatment regimens in acute myeloid leukaemia with a high proliferative activity
    J Braess
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Br J Haematol 110:170-9. 2000
    ..077)...
  12. doi Targeted next-generation sequencing detects point mutations, insertions, deletions and balanced chromosomal rearrangements as well as identifies novel leukemia-specific fusion genes in a single procedure
    V Grossmann
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 25:671-80. 2011
    ..This assay has the strong potential to become an important method for the comprehensive genetic characterization of particular leukemias and other malignancies harboring complex genomes...
  13. doi SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations
    M Meggendorfer
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 27:1852-60. 2013
    ..001 for both) and were mutually exclusive of JAK2 and TET2 mutations. In conclusion, SETBP1mut add an important new diagnostic marker for MDS/MPN and in particular for aCML. ..
  14. ncbi Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML
    C Schoch
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Leukemia 18:120-5. 2004
    ..In conclusion, these data indicate that cytogenetics are an important prognostic parameter in t-AML. Furthermore, t-AML is an unfavorable factor independent of cytogenetics with respect to survival...
  15. doi Characterization of NPM1-mutated AML with a history of myelodysplastic syndromes or myeloproliferative neoplasms
    S Schnittger
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 25:615-21. 2011
    ..Thus, NPM1 mutations are involved in the transformation from MDS to AML or MPN to blast phase in single cases, which should be further confirmed in larger studies...
  16. ncbi The role of different genetic subtypes of CEBPA mutated AML
    A Fasan
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 28:794-803. 2014
    ..020). Outcome in CEBPAsm cases strongly depended on concurrent FLT3-ITD. In conclusion, we propose that only CEBPAdm should be considered as an entity in the WHO classification of AML and should be clearly distinguished from CEBPAsm AML...
  17. ncbi Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG
    M Fiegl
    Department of Internal Medicine III, University Hospital of Munich, Munich, Germany
    Leukemia 28:1001-7. 2014
    ..01). In conclusion, fludarabine has a beneficial, although moderate, impact on the antileukemic efficacy of high-dose cytarabine-based salvage therapy for relapsed and refractory AML...
  18. doi SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients
    S Jeromin
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 28:108-17. 2014
    ..Finally, our data suggest that analysis of gene mutations refines the risk stratification of cytogenetic prognostic subgroups and confirms data of a recently proposed model integrating molecular and cytogenetic data. ..
  19. doi ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome
    S Schnittger
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 27:82-91. 2013
    ..032, relative risk: 1.70). In conclusion, ASXL1mut belong to the most frequent mutations in intermediate risk group AML. Their strong and independent dismal prognostic impact suggests the inclusion into the diagnostic work-up of AML...
  20. ncbi Pediatric acute lymphoblastic leukemia (ALL) gene expression signatures classify an independent cohort of adult ALL patients
    A Kohlmann
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig Maximilians University, Munich, Germany
    Leukemia 18:63-71. 2004
    ..As such, previously reported gene expression patterns identified by microarray technology are validated and confirmed on truly independent leukemia patient samples...
  21. ncbi New insights into the biology of acute myeloid leukemia and their impact on treatment
    W Hiddemann
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University Munich
    Verh Dtsch Ges Pathol 87:72-8. 2003
    ..Gene expression profiling therefore opens a new and exciting perspective in leukemia biology and therapy that may have substantial impact on the improvement of diagnosis and more importantly may guide therapeutic strategies...
  22. ncbi Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162
    S Schnittger
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 21:725-31. 2007
    ..0203). Immunophenotype revealed lower CD2, CD13, CD33 and CD90 levels than in type A fusion cases (P=0.036, 0.002, 0.029 and 0.045, respectively). However, the type of fusion was not an independent prognostic parameter...
  23. ncbi Gain of an isochromosome 5p: a new recurrent chromosome abnormality in acute monoblastic leukemia
    C Schoch
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Marchioninistrass 15, 81377 Munich, Germany
    Cancer Genet Cytogenet 127:85-8. 2001
    ..As an isochromosome 5p can be misinterpreted as a deletion 5q, which occurs frequently in AML, fluorescence in situ hybridization with loci specific probes is a helpful method to detect this rare abnormality...
  24. ncbi Use of five-color staining improves the sensitivity of multiparameter flow cytomeric assessment of minimal residual disease in patients with acute myeloid leukemia
    D Voskova
    MLL Munich Leukemia Laboratory, Muenchen, Germany
    Leuk Lymphoma 48:80-8. 2007
    ..25) at the follow-up checkpoint corresponded to a longer event-free survival. These data suggest that the application of five-color staining significantly improves the sensitivity and accuracy of the method...
  25. ncbi Genomic gains and losses influence expression levels of genes located within the affected regions: a study on acute myeloid leukemias with trisomy 8, 11, or 13, monosomy 7, or deletion 5q
    C Schoch
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Leukemia 19:1224-8. 2005
    ..Losses of specific regions of the genome determine the gene expression profile more strongly than the gain of whole chromosomes...
  26. ncbi Proliferative activity of leukaemic blasts and cytosine arabinoside pharmacodynamics are associated with cytogenetically defined prognostic subgroups in acute myeloid leukaemia
    J Braess
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Br J Haematol 113:975-82. 2001
    ....
  27. ncbi Impact of FLT3 mutations and promyelocytic leukaemia-breakpoint on clinical characteristics and prognosis in acute promyelocytic leukaemia
    Florian Kuchenbauer
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig Maximilians University of Munich, University Hospital Grosshadern, Munich, Germany
    Br J Haematol 130:196-202. 2005
    ..6%) and associated with a significant lower overall survival (P = 0.0339). In addition, cases with bcr3 showed a tendency for a worse event-free survival (P = 0.0795) compared with the bcr1 group...
  28. doi Monitoring of residual disease by next-generation deep-sequencing of RUNX1 mutations can identify acute myeloid leukemia patients with resistant disease
    A Kohlmann
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 28:129-37. 2014
    ..The measurement of mutation load may refine the assignment into distinct risk categories and treatment strategies...
  29. ncbi Efficacy of fludarabine, intermittent sequential high-dose cytosine arabinoside, and mitoxantrone (FIS-HAM) salvage therapy in highly resistant acute leukemias
    W Kern
    University Hospital Grosshadern, Department of Medicine III, Ludwig Maximilians University, Munich, Germany
    Ann Hematol 80:334-9. 2001
    ..However, due to its pronounced toxicity, this regimen should be restricted to third-line therapy for patients expecting a suitable donor for allogeneic transplantation, and supportive treatment should be optimized...
  30. ncbi Leukaemic blasts differ from normal bone marrow mononuclear cells and CD34+ haemopoietic stem cells in their metabolism of cytosine arabinoside
    J Braess
    Medical Clinic III, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
    Br J Haematol 105:388-93. 1999
    ..These data suggest a metabolic basis for the relative selectivity of AraC cytotoxicity for AML blasts and provide a means to determine the role of different metabolites and their related mechanism of action for overall AraC cytotoxicity...
  31. ncbi Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia
    M Weisser
    Laboratory for Leukemia Diagnostics, Medical Department III, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
    Leukemia 19:1416-23. 2005
    ..An increase of WT1 levels was detected in 16/44 cases, which subsequently relapsed within a median of 38 days (range 8--180 days). In conclusion, quantification of WT1 may be used for MRD studies and for prognostification in AML...
  32. ncbi Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia
    S Schnittger
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 25:1297-304. 2011
    ..009 for EFS, P=0.008 for OS). In conclusion, for risk estimation in NPM1 mutated AML not only the FLT3-ITD status, but also the FLT3-ITD load has to be taken into account. These data might contribute to clinical decision making in AML...
  33. ncbi Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping
    C Haferlach
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 21:2442-51. 2007
    ..Therefore, prospective clinical trials should evaluate the prognostic impact of newly available CBA data...
  34. doi The detection of TP53 mutations in chronic lymphocytic leukemia independently predicts rapid disease progression and is highly correlated with a complex aberrant karyotype
    F Dicker
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 23:117-24. 2009
    ..9 months, P<0.001). In multivariate Cox regression analysis, VH status, TP53 mutations and also isolated TP53 mutations independently predicted rapid disease progression...
  35. doi Landscape of TET2 mutations in acute myeloid leukemia
    S Weissmann
    MLL Munich Leukemia Laboratory, Munich, Germany
    Leukemia 26:934-42. 2012
    ..3 vs 41.3 months, P=0.048). These data support a role for TET2 as an important prognostic biomarker in AML...
  36. ncbi Microalbuminuria during cisplatin therapy: relation with pharmacokinetics and implications for nephroprotection
    W Kern
    University Hospital Grosshadern, Department of Medicine III, Ludwig Maximilians University, Munchen, Germany
    Anticancer Res 20:3679-88. 2000
    ..To assess the relation of cisplatin-induced nephrotoxicity to its pharmacology...
  37. ncbi Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype
    C Haferlach
    MLL Munich Leukemia Laboratory, Max Lebsche Platz, Munich, Germany
    Leukemia 22:1539-41. 2008
    ..We confirmed a high incidence of TP53 mutations in AML with a complex aberrant karyotype (29/42, 69%) and demonstrated that TP53 mutations are very rare in AML without a complex aberrant karyotype (4/193, 2.1%)...
  38. ncbi Towards a pathogenesis-oriented therapy of acute myeloid leukemia
    W Hiddemann
    Department of Internal Medicine III, University of Munich Grosshadern, Marchioninistr 15, München 81377, Germany
    Crit Rev Oncol Hematol 56:235-45. 2005
    ..The first steps towards this goal have been taken and give rise to the hope for more effective and more specific therapies of AML...
  39. ncbi [Diagnostics and therapy of acute myeloid leukemia]
    W Kern
    Klinikum der Universitat Munchen Grosshadern, Medizinische Klinik III, Munchen
    Dtsch Med Wochenschr 127:2208-13. 2002
  40. ncbi Comparison of mRNA abundance quantified by gene expression profiling and percentage of positive cells using immunophenotyping for diagnostic antigens in acute and chronic leukemias
    Wolfgang Kern
    MLL Munich Leukemia Laboratory, Munich, Germany
    Cancer 107:2401-7. 2006
    ....
  41. ncbi Loss of genetic material is more common than gain in acute myeloid leukemia with complex aberrant karyotype: a detailed analysis of 125 cases using conventional chromosome analysis and fluorescence in situ hybridization including 24-color FISH
    Claudia Schoch
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Genes Chromosomes Cancer 35:20-9. 2002
    ....
  42. pmc Landscape of genetic lesions in 944 patients with myelodysplastic syndromes
    T Haferlach
    Munich Leukemia Laboratory MLL, Munich, Germany
    Leukemia 28:241-7. 2014
    ..001 each). Thus, large-scale genetic and molecular profiling of multiple target genes is invaluable for subclassification and prognostication in MDS patients. ..
  43. ncbi Discrimination of chronic lymphocytic leukemia (CLL) and CLL/PL by cytomorphology can clearly be correlated to specific genetic markers as investigated by interphase fluorescence in situ hybridization (FISH)
    U Bacher
    Laboratory for Leukemia Diagnostics, Department for Internal Medicine III, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistr 15, 81377, Munich, Germany
    Ann Hematol 83:349-55. 2004
    ....
  44. ncbi Molecular characterization of acute leukemias by use of microarray technology
    Alexander Kohlmann
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig Maximilians University, Munich, Germany
    Genes Chromosomes Cancer 37:396-405. 2003
    ..These data support a possible future application of microarray technology for classification of the acute leukemias...
  45. doi Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML
    Susanne Schnittger
    MLL Munich Leukemia Laboratory, Munich, Germany
    Blood 114:2220-31. 2009
    ..Similar results were obtained in patients undergoing second-line chemotherapy or allogeneic stem cell transplantation...
  46. doi Toward a comprehensive prognostic scoring system in chronic lymphocytic leukemia based on a combination of genetic parameters
    Claudia Haferlach
    MLL Munich Leukemia Laboratory, Munich, Germany
    Genes Chromosomes Cancer 49:851-9. 2010
    ..The proposed scoring systems for OS and TTT based on a combination of genetic markers improve the separation of prognostic subgroups in CLL already early in the course of the disease...
  47. ncbi Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve
    W Kern
    University Hospital Grosshadern, Department of Medicine III, Ludwig Maximilians University, Munchen, Germany
    J Cancer Res Clin Oncol 127:64-8. 2001
    ..To further define the most appropriate way of choosing the dose of carboplatin...
  48. ncbi Modern diagnostics in chronic myeloproliferative diseases (CMPDs)
    T Haferlach
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Marchioninistreet 15, 81377 Munich, Germany
    Ann Hematol 83:S59-61. 2004
    ....
  49. ncbi Genetic classification of acute myeloid leukemia (AML)
    T Haferlach
    Laboratory for Leukemia Diagnostics, Dept of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Ann Hematol 83:S97-100. 2004
    ....
  50. ncbi Monitoring of minimal residual disease in acute myeloid leukemia
    Wolfgang Kern
    MLL Munich Leukemia Laboratory, Munich, Germany
    Cancer 112:4-16. 2008
    ..Large clinical trials will determine the exact role and place of immunologic and RQ-PCR-based monitoring of MRD in the therapy of patients with AML...
  51. ncbi Diagnostic pathways in acute leukemias: a proposal for a multimodal approach
    Torsten Haferlach
    MLL Munich Leukemia Laboratory, Munich, Germany
    Ann Hematol 86:311-27. 2007
    ....
  52. doi Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as "AML not otherwis
    Miriam Miesner
    MLL Munich Leukemia Laboratory, Munich, Germany
    Blood 116:2742-51. 2010
    ..Thus, MLD alone showed no independent clinical effect, whereas cytogenetics and MDS history were prognostically relevant...
  53. ncbi Trisomy 13 is strongly associated with AML1/RUNX1 mutations and increased FLT3 expression in acute myeloid leukemia
    Frank Dicker
    Munich Leukemia Laboratory GmbH, Munich, Germany
    Blood 110:1308-16. 2007
    ..The results of the present study indicate that in the absence of FLT3 mutations, FLT3 overexpression might be a mechanism for FLT3 activation, which cooperates with RUNX1 mutations in leukemogenesis...
  54. ncbi Role of gene expression profiling for diagnosing acute leukemias
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Munich, Germany
    Rev Clin Exp Hematol 9:E1. 2005
    ..Furthermore, it is anticipated that new biologically defined and clinically relevant subtypes of leukemia will be identified based on gene expression profiling. This method may therefore guide therapeutic decisions...
  55. ncbi Monitoring of minimal residual disease in acute myeloid leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Ludwig Maximilians University, University Hospital Grosshadern, Department of Internal Medicine III, 81366 Muenchen, Germany
    Crit Rev Oncol Hematol 56:283-309. 2005
    ..Thus, it is desirable to establish new molecular markers for PCR-based studies. Large clinical trials will determine the role and place of immunologic and PCR-based monitoring in the prognostic stratification of patients with AML...
  56. ncbi Risk-adapted therapy of AML: the AMLCG experience
    W Kern
    Medizinische Klinik III, Klinikum der Universitat, Grosshadern, Germany
    Ann Hematol 83:S49-51. 2004
    ..These results underline the need for large comprehensive trials to allow the detection of therapy effects in biologically defined subgroups of AML...
  57. ncbi Cytidine deaminase - the methodological relevance of AraC deamination for ex vivo experiments using cultured cell lines, fresh leukemic blasts, and normal bone marrow cells
    J Braess
    Medical Clinic III, Forschungslabor A, Klinikum Grosshadern, D 81377 Munich, Germany
    Ann Hematol 78:514-20. 1999
    ..g., 35.6 ng/10(7) cells in REH versus 180.2 ng/10(7) cells in BLIN cells). In contrast to permanent cell lines, fresh leukemic blasts and normal bone marrow mononuclear cells featured low AraC degradation in the model system...
  58. doi Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial
    H Schmidt
    Dr von Hauner Children s Hospital, University of Munich, Lindwurmstr 4, 80337 Munich, Germany
    J Med Genet 46:217-22. 2009
    ..Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease...
  59. ncbi Oxaliplatin pharmacokinetics during a four-hour infusion
    W Kern
    Ludwig Maximilians University Hospital Grosshadern, Department of Medicine III, Munchen, Germany
    Clin Cancer Res 5:761-5. 1999
    ....
  60. ncbi Further correlations of morphology according to FAB and WHO classification to cytogenetics in de novo acute myeloid leukemia: a study on 2,235 patients
    Ulrike Bacher
    Laboratory for Leukemia Diagnostics, Department for Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Marchioninistr 15, 81377, Munich, Germany
    Ann Hematol 84:785-91. 2005
    ..In conclusion, the central role of morphology as defined by the FAB and WHO classification in AML at diagnosis is still justified in combination with other techniques...
  61. ncbi Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype
    Susanne Schnittger
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilian s University, Munich, Germany
    Blood 106:3733-9. 2005
    ..In conclusion, this study demonstrates that NPM1+/FLT3-LM- mutations are an independent predictor for a favorable outcome in AML with normal karyotype...
  62. ncbi Population-based age-specific incidences of cytogenetic subgroups of acute myeloid leukemia
    Ulrike Bacher
    Department for Internal Medicine III, Klinikum, Grosshadern, Ludwig Maximilians University, Munich, Germany
    Haematologica 90:1502-10. 2005
    ..However, detailed data on the population-based age-dependent incidences of distinct cytogenetic subtypes as well as of molecular mutations are lacking...
  63. ncbi D324N single-nucleotide polymorphism in the FLT3 gene is associated with higher risk of myeloid leukemias
    Susanne Schnittger
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Munich, Germany
    Genes Chromosomes Cancer 45:332-7. 2006
    ..001). In addition, 21 of 234 CML (9.0%) and 7 of 155 ALL (4.5%) cases carried the FLT3 D324N. Our data suggest that the FLT3 D324N variant might be associated with a predisposition to different subtypes of leukemia...
  64. doi Dose-dense induction with sequential high-dose cytarabine and mitoxantone (S-HAM) and pegfilgrastim results in a high efficacy and a short duration of critical neutropenia in de novo acute myeloid leukemia: a pilot study of the AMLCG
    Jan Braess
    Department of Internal Medicine III, Laboratory for Leukemia Diagnostics, Klinikum Grosshadern der LMU, Munchen, Germany
    Blood 113:3903-10. 2009
    ....
  65. ncbi Evaluation of complete disease remission in acute myeloid leukemia: a prospective study based on cytomorphology, interphase fluorescence in situ hybridization, and immunophenotyping during follow-up in patients with acute myeloid leukemia
    Ulrike Bacher
    Laboratory for Leukemia Diagnostics, Department for Internal Medicine III, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
    Cancer 106:839-47. 2006
    ..The detection of minimal residual disease (MRD) for predicting prognosis and for therapeutic planning still are under discussion...
  66. ncbi A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia
    Ulrike Bacher
    Department of Clinical Chemistry, Ludwig Maximilians University, Munich Marchioninistr 15, 81377 Munich
    Haematologica 91:817-20. 2006
    ..A FIP1L1-PDGFRA fusion gene was identified in four male patients by interphase FISH and RT-PCR. These methods in combination demonstrated clonality in 8/40 patients (20%) with a male predominance (6/8; 75%)...
  67. ncbi Acute myeloid leukemia (AML) with t(8;21)(q22;q22) relapsing as AML with t(3;21)(q26;q22)
    Ulrike Bacher
    Department of Clinical Chemistry, Ludwig Maximilians University of Munich, Marchioninistrasse 15, 81377 Munich, Germany
    Cancer Genet Cytogenet 168:172-4. 2006
    ..These data suggest that this patient developed a secondary therapy-related AML rather than a relapse...
  68. ncbi Implications of NRAS mutations in AML: a study of 2502 patients
    Ulrike Bacher
    Munich Leukemia Laboratory, Department of Internal Medicine III, University Hospital Munich, Ludwig Maximilians University, Max Lebsche Platz 31, 81377 Munich, Germany
    Blood 107:3847-53. 2006
    ..However, there was a trend to better survival in most subgroups, especially when other molecular markers (FLT3-LM, MLL-PTD, and NPM) were taken into account...
  69. ncbi Impact of integrating clinical and genetic information
    Martin Dugas
    Department of Medical Informatics, Biometrics and Epidemiology IBE, University of Munich, Marchioninistr 15, D 81377 Munich, Germany
    In Silico Biol 2:383-91. 2002
    ....
  70. ncbi Correlation of protein expression and gene expression in acute leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Ludwig Maximilians University, University Hospital Grosshadern, Department of Internal Medicine III, Munich, Germany
    Cytometry B Clin Cytom 55:29-36. 2003
    ..In the future, diagnostic procedures may include oligonucleotide microarray analysis (MA) to detect expression patterns of large numbers of specific genes...
  71. ncbi FLT3 length mutations as marker for follow-up studies in acute myeloid leukaemia
    Susanne Schnittger
    Laboratory for Leukaemia Diagnostics, Department of Internal Medicine III, Ludwig Maximilians University of Munich, University Hospital Grosshadern, Munich, Germany
    Acta Haematol 112:68-78. 2004
    ..Using conventional PCR it clearly could be shown that for most of the patients positive at presentation FLT3-LM is a reliable PCR marker for monitoring treatment response. Even an early detection of relapse was possible in some cases...
  72. ncbi Prognostic impact of early response to induction therapy as assessed by multiparameter flow cytometry in acute myeloid leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Dept of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, 81366 Muenchen, Germany
    Haematologica 89:528-40. 2004
    ..We improved the identification of this parameter by implementing multiparameter flow cytometry to quantify bone marrow cells carrying leukemia-associated immunophenotypes (LAIP)...
  73. ncbi A new prognostic score for patients with acute myeloid leukemia based on cytogenetics and early blast clearance in trials of the German AML Cooperative Group
    Torsten Haferlach
    Ludwig Maximilians University, University Hospital Grosshadern, Dept of Internal Medicine III, Munchen, Germany
    Haematologica 89:408-18. 2004
    ..To refine cytogenetically based risk-stratification in acute myeloid leukemia (AML)...
  74. pmc Acute myeloid leukemias with reciprocal rearrangements can be distinguished by specific gene expression profiles
    Claudia Schoch
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, 81366 Munich, Germany
    Proc Natl Acad Sci U S A 99:10008-13. 2002
    ..By using two different strategies for microarray data analyses, this study revealed a unique correlation between AML-specific cytogenetic aberrations and gene expression profiles...
  75. ncbi Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124 patients
    Torsten Haferlach
    Department of Internal Medicine III, Laboratory for Leukaemia Diagnostics, University Hospital Grosshadern, Ludwig Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany
    Br J Haematol 118:426-31. 2002
    ..In conclusion, we demonstrated genetic, i.e. biological, differences between AML M5a and AML M5b and all other AML. Therefore, AML M5 should further be categorized as two different groups, as proposed by the WHO classification...
  76. ncbi Rapid diagnostic approach to PML-RARalpha-positive acute promyelocytic leukemia
    Claudia Schoch
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Hematol J 3:259-63. 2002
    ..The introduction of all trans retinoic acid (ATRA) into treatment protocols has improved the outcome of APL dramatically. Therefore, it is essential to establish the diagnosis of APL as quickly and as reliably as possible...
  77. ncbi Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial
    Wolfgang Kern
    Ludwig Maximilians University, University Hospital Grosshadern, Department of Internal Medicine III, Muenchen, Germany
    Blood 101:64-70. 2003
    ..0001), LDH (P <.0001), and day 16 blasts (P =.0359). The prognostic significance of day 16 blasts is independent of pretherapeutic parameters and predicts outcome even in patients achieving a CR...
  78. ncbi Gene expression profiling as a tool for the diagnosis of acute leukemias
    Torsten Haferlach
    Department of Internal Medicine III, University Hospital Grosshadern, Munich, Germany
    Semin Hematol 40:281-95. 2003
    ..Gene expression profiling should also lead to the detection of new biological and clinically relevant subtypes in leukemia and therefore guide therapeutic decisions...
  79. ncbi Adverse reactions to oxaliplatin: a retrospective study of 25 patients treated in one institution
    Georg Lenz
    Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Anticancer Drugs 14:731-3. 2003
    ..Pre-medication was ineffective in preventing further reactions and consequently the treatment regimen had to be changed in all cases...
  80. ncbi Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML
    Torsten Haferlach
    Department of Medicine III, Ludwig Maximilians University, Grosshadern, Munich, Germany
    J Clin Oncol 21:256-65. 2003
    ..We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification...
  81. ncbi Monitoring of acute myeloid leukemia by flow cytometry
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Ludwig Maximilians University, University Hospital Grosshadern, Department of Internal Medicine III, 81366 Munich, Germany
    Curr Oncol Rep 5:405-12. 2003
    ..Large clinical trials will determine the role of immunologic monitoring in the prognostic stratification of patients with AML...
  82. ncbi New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts
    Susanne Schnittger
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany
    Blood 102:2746-55. 2003
    ..By combining the transcription ratios at these 2 checkpoints, a new powerful prognostic score has been established...
  83. ncbi AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases
    Claudia Schoch
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University of Munich, Marchioninistr 15, 81377 Munchen, Germany
    Blood 102:2395-402. 2003
    ..0 vs 8.9 months, P =.36). In conclusion, the category AML with 11q23/MLL abnormalities accounts for 2.8% of unselected AML, is closely associated with monocytic differentiation, and has a dismal prognosis. (..
  84. ncbi Detection of minimal residual disease in unselected patients with acute myeloid leukemia using multiparameter flow cytometry for definition of leukemia-associated immunophenotypes and determination of their frequencies in normal bone marrow
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Ludwig Maximilians University, University Hospital Grosshadern, Dept of Internal Medicine III, Muenchen, Germany
    Haematologica 88:646-53. 2003
    ..The present analysis aimed at improving the applicability of this approach to more patients with AML...
  85. ncbi Application of cisplatin as intraoperative hyperthermic peritoneal lavage (IHPL) in patients with locally advanced gastric cancer: analysis of pharmacokinetics and of nephrotoxicity
    Wolfgang Kern
    University Hospital Grosshadern, Department of Internal Medicine III, Ludwig Maximilians University, 81366 München, Germany
    Anticancer Res 22:3099-102. 2002
    ..The purpose of this study was to assess the extent of the systemic absorption of cisplatin during intraoperative hyperthermic peritoneal lavage (IHPL) in patients with locally advanced gastric cancer...
  86. ncbi Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease
    Susanne Schnittger
    Department of Internal Medicine III, University of Munich, Germany
    Blood 100:59-66. 2002
    ..6 months; P =.0072) because of a higher relapse rate. Besides the importance of FLT3-LM for biologic and clinical characterization of AML, we show its value as a marker for disease monitoring based on 120 follow-up samples of 34 patients...
  87. ncbi The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups
    Claudia Schoch
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Haematologica 89:1082-90. 2004
    ..The 1225 patients with de novo AML were separated according to age as follows: A1: 16 to 49 years (n=442), A2: 50 to 59 years (n=246), A3: 60-69 years (n=333), A4: 70 years and older (n=204)...
  88. ncbi AML M3 and AML M3 variant each have a distinct gene expression signature but also share patterns different from other genetically defined AML subtypes
    Torsten Haferlach
    Laboratory for Leukemia Diagnostics, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Genes Chromosomes Cancer 43:113-27. 2005
    ..0001), may partly contribute to the different phenotypes. However, linear regression analysis demonstrated that genes differentially expressed between M3 and M3v did not correlate with FLT3-LM...
  89. ncbi Additional clonal abnormalities in Philadelphia-positive ALL and CML demonstrate a different cytogenetic pattern at diagnosis and follow different pathways at progression
    Ulrike Bacher
    Laboratory for Leukemia Diagnostics, Department for Internal Medicine III, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistrasse 15, D 81377 Munich, Germany
    Cancer Genet Cytogenet 157:53-61. 2005
    ..In conclusion, we were able to demonstrate that the cytogenetic patterns of Ph+ ALL and of CML are different at diagnosis and furthermore follow different pathways during progression or relapse...
  90. ncbi Conventional cytogenetics of myeloproliferative diseases other than CML contribute valid information
    Ulrike Bacher
    Laboratory for Leukemia Diagnostics, Department for Internal Medicine III, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany
    Ann Hematol 84:250-7. 2005
    ..In ET and in HES the aberration rate was only 3 and 7%, respectively. Thus, cytogenetics can be omitted. However, in some of these cases molecular procedures should be integrated into the routine diagnostic process...
  91. ncbi Acute myeloid leukemia with a complex aberrant karyotype is a distinct biological entity characterized by genomic imbalances and a specific gene expression profile
    Claudia Schoch
    Laboratory for Leukemia Diagnostics, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Genes Chromosomes Cancer 43:227-38. 2005
    ..These data may be the basis for developing targeted therapeutic strategies to increase the cure rate in patients with AML and a complex aberrant karyotype...
  92. ncbi Global approach to the diagnosis of leukemia using gene expression profiling
    Torsten Haferlach
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig Maximilians University, Marchioninistr 15, 81377 Munich
    Blood 106:1189-98. 2005
    ..Accordingly, cluster analysis completely separated all 13 subgroups analyzed. Gene expression profiling can predict all clinically relevant subentities of leukemia with high accuracy...
  93. ncbi Blast count and cytogenetics correlate and are useful parameters for the evaluation of different phases in chronic myeloid leukemia
    Ulrike Bacher
    Laboratory for Leukemia Diagnostics, Department for Internal Medicine III, Klinikum Grossharden, Ludwig Maximilians University, Marchioninistr, Munich, Germany
    Leuk Lymphoma 46:357-66. 2005
    ..We therefore propose to focus staging systems of CML on the correlation of the percentage of bone marrow blasts and the cytogenetic results...
  94. ncbi Risk assessment by monitoring expression levels of partial tandem duplications in the MLL gene in acute myeloid leukemia during therapy
    Martin Weisser
    Laboratory for Leukemia Diagnostics, Medical Department III, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
    Haematologica 90:881-9. 2005
    ....
  95. pmc The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice
    Christina Schessl
    Clinical Cooperative Group Leukemia, National Research Center for Environment and Health GSF, Munich, Germany
    J Clin Invest 115:2159-68. 2005
    ....
  96. ncbi Pattern robustness of diagnostic gene expression signatures in leukemia
    Alexander Kohlmann
    Laboratory for Leukemia Diagnostics, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Genes Chromosomes Cancer 42:299-307. 2005
    ....
  97. ncbi Cytogenetic profile in de novo acute myeloid leukemia with FAB subtypes M0, M1, and M2: a study based on 652 cases analyzed with morphology, cytogenetics, and fluorescence in situ hybridization
    Mirjam Klaus
    Department of Internal Medicine III, Laboratory for Leukemia Diagnostics, Ludwig Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany
    Cancer Genet Cytogenet 155:47-56. 2004
    ..In conclusion, t(8;21), +11, +13, and +14 are strongly associated with AML M0, M1, and M2. The FISH screening analyses identified abnormalities in an additional 3% in normal karyotypes...
  98. ncbi Stability of leukemia-associated aberrant immunophenotypes in patients with acute myeloid leukemia between diagnosis and relapse: comparison with cytomorphologic, cytogenetic, and molecular genetic findings
    Daniela Voskova
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Munich, Germany
    Cytometry B Clin Cytom 62:25-38. 2004
    ..Changes in LAIPs during the course of the disease may be a limitation for this approach...
  99. ncbi Four-fold staining including CD45 gating improves the sensitivity of multiparameter flow cytometric assessment of minimal residual disease in patients with acute myeloid leukemia
    Wolfgang Kern
    Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig Maximilians University, University Hospital Grosshadern, 81366 Muenchen, Germany
    Hematol J 5:410-8. 2004
    ..08 log (range, 1.22-4.01) and 2.28 log (range, 1.12-3.34) with and without CD45 gating. CD45 gating improves the sensitivity of MFC-based MRD monitoring in AML by 1 log...
  100. ncbi Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy
    W Kern
    Ludwig Maximilians University, University Hospital Grosshadern, Dept of Internal Medicine III, Muenchen, Germany
    Leukemia 16:2084-91. 2002
    ..002). These data suggest that the instability of the karyotype between diagnosis and relapse and thus karyotype aberrations at relapse in particular contribute to the refractoriness of AML to anti-leukemic therapy...
  101. ncbi Detection and separation of the S-adenosylmethionine-decarboxylase inhibitor SAM486A in human plasma and urine by reversed-phase ion-pairing high-performance liquid chromatography
    W Kern
    University Hospital Grosshadern, Department of Medicine III, Ludwig Maximilians University, Munchen, Germany
    J Pharmacol Toxicol Methods 45:175-80. 2001
    ..0) as eluent. Analysis time was 23.0 +/- 0.1 min. The separation parameters were: capacacity factor = 6.21; plates/m = 15,002; peak tailing = 2.076. The method is linear between 5 ng/ml (detection limit) and 1000 ng/ml...