Immune response to the ALK oncogenic tyrosine kinase in patients with anaplastic large-cell lymphoma

Oncogenic anaplastic lymphoma kinase (ALK) fusion proteins (nucleophosmin-A LK [NPM-ALK] and other variants) are expressed in many cases of anaplastic large-cell lymphoma (ALCL) but are absent from normal tissues. The possibil ity that ALK proteins are immunogenic was investigated with the use of an i mmunocytochemical technique to screen plasma from ALK-positive ALCL on tran sfectants expressing ALK proteins and by an in vitro kinase assay. Circulat ing antibodies against NPM-ALK protein were present in all ALK-positive ALC L patients (11 out of 11 cases) studied while 10 patients also had antibodi es recognizing normal ALK protein. Weak antibodies reactive with NPM-ALK (w hich may represent anti-NPM autoantibodies) were detected by the in vitro k inase assay in 3 of the 10 control samples (but not by immunocytochemistry) . The presence of anti-ALK antibodies may be relevant to the relatively goo d prognosis of ALK-positive ALCL. The immunocytochemical technique for dete cting anti-ALK activity is simple and semiquantative and may provide a mean s of detecting B-cell responses to other tumor-associated molecules. (Blood . 2000;96: 1605-1607) (C) 2000 by The American Society of Hematology.