title: Prognostic relevance of HER2/neu in acute lymphoblastic leukemia and induction of NK cell reactivity against primary ALL blasts by trastuzumab.
abstract: The epidermal growth factor receptor HER2/neu is expressed on various cancers and represents a negative prognostic marker, but is also a target for the therapeutic monoclonal antibody Trastuzumab. In about 30% of cases, HER2/neu is expressed on acute lymphoblastic leukemia (ALL) cells and was proposed to be associated with a deleterious prognosis. Here we evaluated clinical data from 65 ALL patients (HER2/neu+, n = 17; HER2/neu-, n = 48) with a median follow-up of 19.4 months (range 0.6-176.5 months) and observed no association of HER2/neu expression with response to chemotherapy, disease free or overall survival. In vitro, treatment of primary ALL cells (CD20+HER2/neu+, CD20+HER2/neu- and CD20-HER2/neu-) with Rituximab and Trastuzumab led to activation of NK cells in strict dependence of the expression of the respective antigen. NK reactivity was more pronounced with Rituximab as compared to Trastuzumab, and combined application could lead to additive effects in cases where both antigens were expressed. Besides providing evidence that HER2/neu expression is no risk factor in ALL patients, our data demonstrates that HER2/neu can be a promising target for Trastuzumab therapy in the subset of ALL patients with the potential to improve disease outcome.
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.|Interfacultary Center for Cell Biology, Department for Immunology, Tuebingen, Germany.
authors.forename: Sebastian P
authors.initials: SP
authors.lastname: Haen
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Schmiedel
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Tuebingen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rothfelder
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Tuebingen, Germany.
authors.forename: Bastian J
authors.initials: BJ
authors.lastname: Schmied
authors.affiliation: Interfacultary Center for Cell Biology, Department for Immunology, Tuebingen, Germany.
authors.forename: Truong-Minh
authors.initials: TM
authors.lastname: Dang
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.|Interfacultary Center for Cell Biology, Department for Immunology, Tuebingen, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Mirza
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Möhle
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.
authors.forename: Wichard
authors.initials: W
authors.lastname: Vogel
authors.affiliation: University Hospital Tuebingen, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Tuebingen, Germany.
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Salih
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use; D000068878:Trastuzumab / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000069283:Rituximab; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: ADCC; HER2/neu; acute lymphoblastic leukemia; rituximab; trastuzumab