[1403] 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, NOS63/69 (91.3%)
ALCL11/27 (40.7%)
CLL55/85 (64.7%)
FL13/60 (21.6%)
DLBCL, GC10/21 (47.6%)
DLBCL, nonGC43/70 (61.4%)

Conclusions: Our study demonstrates that CD48 is aberrantly downregulated in ALCLs (40.7%) compared to PTCL, NOS (91.3%, p<0.001). The loss of CD48 expression in ALCL maybe related to the deficiency of the TCR-signalosome previously observed in these cases. Interestingly, CD48 is aberrantly overexpressed in FL and DLBCL, GC type relative to reactive GC B-cells. These findings suggest that CD48 may be useful in the workup of ALCL versus PTCL, NOS. In addition, they support future studies of the role of CD48 in ALCL pathogenesis.
Category: Hematopathology

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 167, Tuesday Morning


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