Prognostic relevance of HER2/neu in acute lymphoblastic leukemia and induction of NK cell reactivity against primary ALL blasts by trastuzumab.
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.
['Haen|Sebastian P|SP|', 'Schmiedel|Benjamin J|BJ|', 'Rothfelder|Kathrin|K|', 'Schmied|Bastian J|BJ|', 'Dang|Truong-Minh|TM|', 'Mirza|Nora|N|', 'Möhle|Robert|R|', 'Kanz|Lothar|L|', 'Vogel|Wichard|W|', 'Salih|Helmut R|HR|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D000920:Antibody-Dependent Cell Cytotoxicity D000970:Antineoplastic Agents D018572:Disease-Free Survival D005260:Female D006801:Humans D053208:Kaplan-Meier Estimate D007694:Killer Cells, Natural D008297:Male D008875:Middle Aged D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma D011379:Prognosis D018719:Receptor, ErbB-2 D012189:Retrospective Studies D000069283:Rituximab D000068878:Trastuzumab D016896:Treatment Outcome D055815:Young Adult
HER2/neu acute lymphoblastic leukemia trastuzumab rituximab ADCC