JL1 Antigen Expression on Bone Marrow Lymphoma Cells from Patients With Non-Hodgkin Lymphoma

Abstract

Background: JL1, a CD43 epitope and mucin family cell surface glycoprotein, is expressed on leukemic cells. An anti-JL1 antibody combined with a toxic substance can have targeted therapeutic effects against JL1-positive leukemia; however, JL1 expression on bone marrow (BM) lymphoma cells has not been assessed using flow cytometry. We investigated JL1 expression on BM lymphoma cells from patients with non-Hodgkin lymphoma (NHL) to assess the potential of JL1 as a therapeutic target.

Methods: Patients with BM involvement of mature B-cell (N=44) or T- and natural killer (NK)-cell (N=4) lymphomas were enrolled from May 2015 to September 2016. JL1 expression on BM lymphoma cells was investigated using flow cytometry. Clinical, pathological, and cytogenetic characteristics, and treatment responses were compared according to JL1 expression status.

Results: Of the patients with NHL and BM involvement, 37.5% (18/48) were JL1-positive. Among mature B-cell lymphomas, 100%, 38.9%, 33.3%, 100%, and 25.0% of Burkitt lymphomas, diffuse large B-cell leukemias, mantle cell leukemias, Waldenstrom macroglobulinemia, and other B-cell lymphomas, respectively, were JL1-positive. Three mature T- and NK-cell NHLs were JL1-positive. JL1 expression was associated with age (P=0.045), complete response (P=0.004), and BM involvement at follow-up (P=0.017), but not with sex, performance status, the B symptoms, packed marrow pattern, cytogenetic abnormalities, or survival.

Conclusions: JL1 positivity was associated with superior complete response and less BM involvement in NHL following chemotherapy.

Keywords: Flow cytometry; JL1 expression; Mature B-cell lymphoma; T- and natural killer-cell lymphoma.

Fig. 1. Measurement of JL1 expression on lymphoma cells by flow cytometry in a patient with follicular lymphoma and bone marrow involvement. Mononuclear lymphoma cells were isolated by gating intermediate to bright CD45-APC expression and low SSC (A), CD19⁺ B-lymphoma cells were isolated by gating intermediate to bright CD45-APC and positive CD19-FITC stained cells (B), and the proportion of JL1-expressing lymphoma cells among B-lymphoma cells was calculated using a CD19-FITC vs JL1-PE dot plot (C). The results of JL1 expression analysis are presented as the proportion of JL1-positive cells among gated lymphoma cells (24.3% in this case).

Abbreviations: CD, cluster of differentiation; SSC, side scatter; FSC, forward scatter; PE, phycoerythrin; APC, allophycocyanin.