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(American Journal of Pathology. 1999;154:1657-1663.)
© 1999 American Society for Investigative Pathology

Short Communication

Biochemical Detection of Novel Anaplastic Lymphoma Kinase Proteins in Tissue Sections of Anaplastic Large Cell Lymphoma

Karen Pulford^*, Brunangelo Falini, Jaqueline Cordell^*, Andreas Rosenwald, German Ott, Hans-Konrad Müller-Hermelink, Kenneth A. MacLennan^§, Laurence Lamant^¶, Antonio Carbone^||, Elias Campo^** and David Y. Mason^*

From the Nuffield Department of Clinical Biochemistry and Cellular Science,^*
John Radcliffe Hospital, Oxford, England; Institute of Haematology,
Perugia University, Perugia, Italy; University Institute of Pathology,
Würzburg, Germany; Imperial Cancer Research Fund,^§
Cancer Medical Research Unit, St. James's University Hospital, Leeds, England; Department of Pathology and UPCM-ERS 1590 CNRS,^¶
CHU Purpan, Toulouse, France; Institute of Pathology,||
Centro Riferimento Oncologico Aviano, Aviano, Italy, and Department of Pathology,^**
Hopital Clinico Provincial, University of Barcelona, Barcelona, Spain

The (2;5) translocation, found in many T-cell and null cell anaplastic large cell lymphomas (ALCLs), creates a hybrid gene encoding the 80-kd NPM-ALK protein. Typically neoplastic cells show labeling of both nucleus and cytoplasm for anaplastic lymphoma kinase (ALK) and for the N-terminus of nucleophosmin (NPM). However, 10–20% of cases exhibit cytoplasmic labeling only for ALK, indicating the probable presence of variants of the classical (2;5) translocation that do not involve the NPM gene. We report the detection (using 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 exhibiting 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 NPM-ALK can be detected by sensitive biochemical techniques using routine cryostat sections.

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