Flow Cytometry Study of CD148, a Tyrosine Phosphatase Receptor, in 184 Chronic B Cell Malignancies, Reveals a High Expression in Mantle Cell and Marginal Zone Lymphomas.

Abstract 1923

Poster Board I-946

We recently characterized CD148 as a potential marker for mantle cell lymphoma using mass spectrometry analysis of cell-derived microvesicles in a restricted set of patients (ASH Annual Meeting Abstracts, Nov 2008; 112: 1766). CD148 is a plasma membrane receptor with phosphatase activity related to CD45, composed of an extracellular domain containing 8 fibronectin type II-like domains, a transmembrane region and a single intracellular phosphatase domain. Interestingly, it was recently shown that deletion of the phosphatase domain of CD148 in mice blocks B cell development at the transitional stage, with a dramatic increase of marginal zone B cells. BCR signalling events are also substantially altered in CD148/CD45 doubly deficient mice.

In the present study, we analyzed the expression of CD148 using flow cytometry in a larger group of controls and patients with circulating pathologic B-cells, including 93 chronic lymphocytic leukemia (CLL), 46 small lymphocytic lymphomas with Matutes score inferior or equal to 3 (SLL), 35 MCL, all harboring (11;14) translocation and/or cyclin D1 overexpression, 5 marginal zone lymphomas (MZL), 5 splenic lymphoma with villous lymphocytes (SLVL), as well as 30 controls. Mean fluorescence intensity of direct CD148 staining with phycoerythrin conjugated 143−41 clone was used for expression comparison.

CD148 MFI of the 30 control cells was weak and very homogeneous (mean = 168, SD = 31), as well as in the 93 CLL (mean = 199, SD = 84). SLL cases (n=46) were stained slightly higher (mean = 297, SD = 138) revealing a slight but significant difference with CLL (p<0.01). The results were strikingly different for the MCL group (n=35), in which the mean CD148 MFI was 635 (SD = 358) which is significantly different from CLL, SLL, and SLVL groups (p < 0.001), and from controls (p < 0.001), thus confirming our preliminary results. We observed also a high CD148 MFI in marginal zone lymphoma, that was not different from the values obtained in MCL but very significantly higher than the other groups studied (p<0.001). Staining of MZL is in accordance with the published expression of CD148 in normal marginal zone of human spleen and tonsils using immunochemistry, but normal mantle zone cells are not stained with anti-CD148 antibodies, suggesting an aberrant CD148 expression in this pathology.

The realization of a Receiver operator characteristic test (ROC curve) between MCL and CLL/SLL showed that in our hands a CD148 MFI superior to 383 allows strongly to suspect MCL diagnosis, with 86% specificity (versus CLL and SLL) and a sensitivity of 90%. Then, a high expression of CD148 may lead to karyotype or cyclin D1 expression analysis for a potential MCL diagnosis.

Low CD148 expressing MCL cases need to be more studied, as well as the higher expressing SLL and CLL, because they could represent particular subgroups. Also, CD148 expression needs to be further studied in the different chronic B cell proliferations, notably in MZL, in order to evaluate its usefulness in first line antibodies diagnostic panel.