Prognostic relevance of HER2/neu in acute lymphoblastic leukemia and induction of NK cell reactivity against primary ALL blasts by trastuzumab

TY - JOUR

T1 - Prognostic relevance of HER2/neu in acute lymphoblastic leukemia and induction of NK cell reactivity against primary ALL blasts by trastuzumab

AU - Haen, Sebastian P

AU - Schmiedel, Benjamin J

AU - Rothfelder, Kathrin

AU - Schmied, Bastian J

AU - Dang, Truong-Minh

AU - Mirza, Nora

AU - Möhle, Robert

AU - Kanz, Lothar

AU - Vogel, Wichard

AU - Salih, Helmut R

PY - 2016/3/15

Y1 - 2016/3/15

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibody-Dependent Cell Cytotoxicity/drug effects

KW - Antineoplastic Agents/therapeutic use

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Kaplan-Meier Estimate

KW - Killer Cells, Natural/immunology

KW - Male

KW - Middle Aged

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy

KW - Prognosis

KW - Receptor, ErbB-2/biosynthesis

KW - Retrospective Studies

KW - Rituximab/therapeutic use

KW - Trastuzumab/therapeutic use

KW - Treatment Outcome

KW - Young Adult

U2 - 10.18632/oncotarget.7344

DO - 10.18632/oncotarget.7344

M3 - SCORING: Journal article

C2 - 26887048

VL - 7

SP - 13013

EP - 13030

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 11

ER -