Biochemical detection of novel anaplastic lymphoma kinase proteins in tissue sections of anaplastic large cell lymphoma

The (2;5) translocation, found in many T-cell and null cell anaplastic larg e cell lymphomas (ALCLs), creates a hybrid gene encoding the 80-kd NPM-ALK protein. Typically neoplastic cells show labeling of both nucleus and cytop lasm for anaplastic lymphoma kinase (ALK) and for the N-terminus of nucleop hosmin (NPM). However, 10-20% of cases exhibit cytoplasmic labeling only fo r ALK, indicating the probable presence of variants of the classical (2;5) translocation that do not involve the NPM gene. We report the detection (us ing Western blotting and an in vitro kinase assay) in seven such ALCL cases , of ALK proteins with molecular masses of 85 kd, 97 kd (one case exhibitin g a (2;3)(p23;q21) translocation), 104 kd (one case carried a (1;2)(q21;p23 ) translocation), and 113 kd, Tyrosine kinase activity was detected in four of these proteins, but the N-terminal portion of NPM could not be detected . These results show how ALCL cases that express ALK proteins other than NP M-ALK can be detected by sensitive biochemical techniques using routine cry ostat sections.