Immune response to the ALK oncogenic tyrosine kinase in patients with anaplastic large-cell lymphoma.
Oncogenic anaplastic lymphoma kinase (ALK) fusion proteins (nucleophosmin-ALK [NPM-ALK] and other variants) are expressed in many cases of anaplastic large-cell lymphoma (ALCL) but are absent from normal tissues. The possibility that ALK proteins are immunogenic was investigated with the use of an immunocytochemical technique to screen plasma from ALK-positive ALCL on transfectants expressing ALK proteins and by an in vitro kinase assay. Circulating antibodies against NPM-ALK protein were present in all ALK-positive ALCL patients (11 out of 11 cases) studied while 10 patients also had antibodies recognizing normal ALK protein. Weak antibodies reactive with NPM-ALK (which may represent anti-NPM autoantibodies) were detected by the in vitro kinase assay in 3 of the 10 control samples (but not by immunocytochemistry). The presence of anti-ALK antibodies may be relevant to the relatively good prognosis of ALK-positive ALCL. The immunocytochemical technique for detecting anti-ALK activity is simple and semiquantative and may provide a means of detecting B-cell responses to other tumor-associated molecules. (Blood. 2000;96:1605-1607)
Pulford
K
K
Nuffield Department of Clinical Laboratory Sciences and the Department of Haematology, John Radcliffe Hospital, Oxford, UK. karen.pulford@cellular-science.ox.ac.uk
Falini
B
B
Banham
A H
AH
Codrington
D
D
Roberton
H
H
Hatton
C
C
Mason
D Y
DY
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D019556:COS Cells; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases
D000906:Antibodies; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases