Glycoproteome Analysis of T-Cell Lymphomas Identifies Selective Downregulation of CD48 Expression in Anaplastic Large Cell Lymphomas (ALCL)
Elena Ivan, Yoon Jeon, Farah Keyoumarsi, Dafydd Thomas, Kojo Elenitoba-Johnson, Megan Lim. University of Michigan, Ann Arbor, MI; Seoul National University Hospital, Seoul, Korea
Background: CD48 is a glycosyl phosphatidylinositol linked protein that is widely expressed on hematopoietic cells and functions as a ligand for CD2 and CD244. The CD48-CD2 interaction plays a role in T-cell receptor (TCR) signaling and is important for the normal function of effector T cells. Using mass spectrometry-based glycoproteomic profiling, we identified CD48 as one of the proteins that is selectively absent in ALCL cell lines (ALK+ and ALK-) compared to other T-cell lymphoma cell lines. The expression of CD48 in malignant lymphoma has not been previously reported. Our objective was to evaluate the CD48 expression in a large panel of T and B-cell lymphomas to determine its diagnostic utility.
Design: The expression of CD48 in cell lines was analyzed by Western blot and flow cytometry. Tissue microarrays (TMA) of ALCL (ALK+ and ALK-), peripheral T-cell lymphomas not otherwise specified (PTCL, NOS), chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DLBCL) were used for immunohistochemical analysis. Cases with more than 15% positive neoplastic cells were scored as positive for CD48. Reactive tonsils and spleen were used as control tissues.
Results: Western blot and flow cytometric analysis confirmed the mass spectrometry results and showed absence of CD48 expression in the ALCL cell lines (ALK+ and ALK-) compared to other T cell lymphoma cell lines. In reactive lymphoid tissues, CD48 demonstrated strong expression in the T cell rich areas, weak expression in the mantle zones and absence in the germinal centers. In the lymphoma TMA, CD48 was expressed in 63/69 cases of PTCL, NOS and less frequently in the ALCL lymphomas (11/27). CD48 was also less frequently expressed in germinal center (GC) derived B-cell lymphomas compared to the non-GC B-cell lymphomas.
|PTCL, NOS||63/69 (91.3%)|
|DLBCL, GC||10/21 (47.6%)|
|DLBCL, nonGC||43/70 (61.4%)|