Plasma Cell CD20 Expression: Primary Aberrant Expression or Receptor up-Regulation

CD20 is a trans-membrane protein expressed on mature B cells through all stages of their development. However, its expression is down regulated at the point of differentiation into plasma cells and expressed only in 16-22% of mature plasma cells. CD20 expression on plasma cells has been described with both favorable prognosis in association with translocation t(11;14) and unfavorable prognosis in association with plasma cell leukemia . The incidence of CD20 expression on plasma cells from patients with relapsed/ refractory multiple myeloma is not well stated in literature and not routinely done in this patients' population. Additionally, it is not known if CD20 represents a primary aberrant expression in newly diagnosed cases of multiple myeloma or possibly represents a secondary genetic change at the time of relapse related to hypothesized myeloma stem cells.   

In order to study the above questions, we retrospectively reviewed the medical records of 92 patients with symptomatic MM who underwent ASCT between January 2008 and December 2011. As of July 2012, 38 patients have relapsed. Bone marrow biopsy and flow cytometry results were available for 33 patients at time of diagnosis and relapse. CD20 expression was positive on plasma cells by flow cytometry in 11 out of 33 patients (33%) at time of relapse.  Interestingly, CD20 expression at diagnosis was negative in 4 out of these 11 patients. This up-regulation in CD 20 expression was associated with clonal evolution in two patients (deletion-17 and complex hypo-diploid cytogenetic, respectively). Confirmatory immune-histochemical staining for CD20 was positive only in 2 of these 4 patients.

Conclusion:

CD20 expression on plasma cells at time of relapse/progression can occur in one third of patients with multiple myeloma and may provide an additional therapeutic target. The cause of discrepancy between CD20 expression by flow cytometry and immune-histochemical staining is unclear and suggests that the two methods may be complementary for a comprehensive evaluation of CD20 expression in multiple myeloma.  CD20 up-regulation in patients with relapsed/refractory myeloma who were previously CD20 negative at diagnosis may represent a secondary genetic event heralding a more aggressive disease.  Future prospective studies evaluating CD20 expression on plasma cells at different stages of disease progression may optimize the timing for anti-CD20 therapy while harnessing the concept of colonogeneic myeloma stem cells.