Instability of Immunophenotype in Plasma Cell Myeloma
Instability of Immunophenotype in Plasma Cell Myeloma
Little information has been reported describingantigen stability in plasma cell myeloma. In this study,the expression frequency and stability of 2 potentialtherapeutic targets, CD20 and CD52, along with thefrequently aberrantly expressed CD56 antigen, wereevaluated by flow cytometric analyses in 56 patientswith plasma cell myeloma. Of the 56 patients, 23 (41%)showed immunophenotype change, including CD56in 6 cases, CD20 in 7 cases, and CD52 in 17 cases.Combined CD56/CD52 change was seen in 3 casesand combined CD20/CD52 in 4 cases. No correlationwas found between immunophenotype change and age,sex, stage, plasma cell morphologic features, extent ofmarrow involvement, time between analyses, type oftherapy, or response to therapy. Immunophenotype shiftwas more common in patients with IgA than in patientswith IgG paraprotein. Recognition of lack of stabilityin immunophenotype may be important, especially inantigen-directed treatment decisions and when specificphenotypes are used to detect residual disease.
Plasma cell myeloma (PCM) is a neoplasm characterized by proliferation of a single clone of plasma cells, a monoclonal immunoglobulin, and skeletal destruction. Multiparametric immunophenotyping of PCM by flow cytometry has been incorporated into practice in many laboratories, not only for diagnosis, but also for monitoring residual disease. CD138+, CD38+, and dim CD45 to CD45– staining is common to normal and abnormal plasma cells. Pan–B-cell antigens such as CD19 and CD20 are negative in the majority of normal plasma cells and PCM cases. However, dim expression of CD19 and CD20 can be seen in normal plasma cells, and such expression may also be present in some cases of PCM. Therefore, these antigens are not helpful in differentiating normal from abnormal plasma cells.
Abnormal plasma cells are often identified by flow cytometric analyses based on the presence of monotypic cytoplasmic immunoglobulin light chain and, in a subset of cases, CD56 expression, which only rarely occurs in normal plasma cells. Although flow cytometry is useful to identify abnormal plasma cells, the diagnosis of PCM requires correlation of other laboratory data, clinical findings, and radiologic results.
PCM is currently an incurable disease, although agents such as thalidomide (Thalomid), lenalidomide (Revlimid), and bortezomib (Velcade) have provided effective salvage therapy for end-stage myeloma. Increasing knowledge of tumor biology and immunology has led to the development of immunotherapeutic and immunoregulatory drugs. Many clinical flow cytometry laboratories now assess expression of a number of potential therapeutically relevant targets, or markers (CD20, CD22, CD25, CD52, and CD30), on the neoplastic cells of lymphoid and plasma cell malignancies.
Knowledge of the expression pattern of these potential therapeutic markers at the time of the diagnosis may allow for initiation of antigen/ligand-directed therapy at diagnosis or at relapse without reanalysis of tumor cells. Studies have suggested the possible role of such monoclonal antibody therapies directed against CD20 and CD52 in the subset of PCMs that are positive for these antigens. Clinical trials evaluating the efficacy of rituximab (anti-CD20 monoclonal antibody) in PCM have shown effectiveness in some cases that are CD20+. Although more frequently used in relapsed or refractory chronic lymphocytic leukemia, alemtuzumab (anti-CD52 monoclonal antibody) is also a potential therapeutic target in PCM. Studies have demonstrated heterogeneous CD52 expression in PCM. In addition, alemtuzumab has been shown to exhibit antitumor activity in animals with early-stage PCM.
Many studies have examined the immunoprofile of PCM. However, these studies have primarily focused on diagnostic utility and minimal residual disease monitoring with little information on immunophenotype stability of myeloma cells in individual patients or on stability of potential therapeutic targets. The purpose of this study was to evaluate the expression frequency and stability of 2 potential therapeutic targets, CD20 and CD52, along with the frequently aberrantly expressed CD56 antigen.
Little information has been reported describingantigen stability in plasma cell myeloma. In this study,the expression frequency and stability of 2 potentialtherapeutic targets, CD20 and CD52, along with thefrequently aberrantly expressed CD56 antigen, wereevaluated by flow cytometric analyses in 56 patientswith plasma cell myeloma. Of the 56 patients, 23 (41%)showed immunophenotype change, including CD56in 6 cases, CD20 in 7 cases, and CD52 in 17 cases.Combined CD56/CD52 change was seen in 3 casesand combined CD20/CD52 in 4 cases. No correlationwas found between immunophenotype change and age,sex, stage, plasma cell morphologic features, extent ofmarrow involvement, time between analyses, type oftherapy, or response to therapy. Immunophenotype shiftwas more common in patients with IgA than in patientswith IgG paraprotein. Recognition of lack of stabilityin immunophenotype may be important, especially inantigen-directed treatment decisions and when specificphenotypes are used to detect residual disease.
Plasma cell myeloma (PCM) is a neoplasm characterized by proliferation of a single clone of plasma cells, a monoclonal immunoglobulin, and skeletal destruction. Multiparametric immunophenotyping of PCM by flow cytometry has been incorporated into practice in many laboratories, not only for diagnosis, but also for monitoring residual disease. CD138+, CD38+, and dim CD45 to CD45– staining is common to normal and abnormal plasma cells. Pan–B-cell antigens such as CD19 and CD20 are negative in the majority of normal plasma cells and PCM cases. However, dim expression of CD19 and CD20 can be seen in normal plasma cells, and such expression may also be present in some cases of PCM. Therefore, these antigens are not helpful in differentiating normal from abnormal plasma cells.
Abnormal plasma cells are often identified by flow cytometric analyses based on the presence of monotypic cytoplasmic immunoglobulin light chain and, in a subset of cases, CD56 expression, which only rarely occurs in normal plasma cells. Although flow cytometry is useful to identify abnormal plasma cells, the diagnosis of PCM requires correlation of other laboratory data, clinical findings, and radiologic results.
PCM is currently an incurable disease, although agents such as thalidomide (Thalomid), lenalidomide (Revlimid), and bortezomib (Velcade) have provided effective salvage therapy for end-stage myeloma. Increasing knowledge of tumor biology and immunology has led to the development of immunotherapeutic and immunoregulatory drugs. Many clinical flow cytometry laboratories now assess expression of a number of potential therapeutically relevant targets, or markers (CD20, CD22, CD25, CD52, and CD30), on the neoplastic cells of lymphoid and plasma cell malignancies.
Knowledge of the expression pattern of these potential therapeutic markers at the time of the diagnosis may allow for initiation of antigen/ligand-directed therapy at diagnosis or at relapse without reanalysis of tumor cells. Studies have suggested the possible role of such monoclonal antibody therapies directed against CD20 and CD52 in the subset of PCMs that are positive for these antigens. Clinical trials evaluating the efficacy of rituximab (anti-CD20 monoclonal antibody) in PCM have shown effectiveness in some cases that are CD20+. Although more frequently used in relapsed or refractory chronic lymphocytic leukemia, alemtuzumab (anti-CD52 monoclonal antibody) is also a potential therapeutic target in PCM. Studies have demonstrated heterogeneous CD52 expression in PCM. In addition, alemtuzumab has been shown to exhibit antitumor activity in animals with early-stage PCM.
Many studies have examined the immunoprofile of PCM. However, these studies have primarily focused on diagnostic utility and minimal residual disease monitoring with little information on immunophenotype stability of myeloma cells in individual patients or on stability of potential therapeutic targets. The purpose of this study was to evaluate the expression frequency and stability of 2 potential therapeutic targets, CD20 and CD52, along with the frequently aberrantly expressed CD56 antigen.
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