Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt.
Department of Medical Oncology, Mansoura Oncology Center, Mansoura University, Mansoura, Egypt.
Cancer Invest. 2021 Oct;39(9):777-782. doi: 10.1080/07357907.2021.1964521. Epub 2021 Aug 25.
Multiple myeloma is an incurable hematological malignancy. Currently, the use of proteasome inhibitors could be superior to chemotherapy-based regimen in the treatment of this disease. However, resistance to bortezomib combination therapy still occurs in some patients. So, this research work aims to assess CD69 and CD56 expression in these cases and their relation to the response to therapy.
Immunophenotyping by 4-color multi-parameter flow cytometry was carried out on 98 multiple myeloma cases. Clonal plasma cells were gated by co-expression of CD38 with CD138 with low SSC, negative or dim CD45.
Double negative CD69 and CD56 (47.9%) multiple myeloma cases were associated with high serum β2 microglobulin, creatinine, calcium and low serum albumin. There was also a significant correlation between the absence of these markers with osteolytic lesions and unfavorable cytogenetic t (4;14) ( < 0.001). Moreover, there was a highly significant correlation between CD69- and CD56- with non-response to bortezomib combination therapy in multiple myeloma patients ( < 0.0001). Regression analysis for the prediction of non- response to treatment in these cases using different prognostic indicators revealed that high serum β2 microglobulin, unfavorable cytogenetic, advanced stage, and low expression of CD69 and CD56 were poor predictors of non-response.
CD69 in association with CD56 could be an independent prognostic factor in multiple myeloma cases. It could be used in the routine laboratory assessment for refining stratification and timely therapeutic decision for highly cost therapy in developing countries.
多发性骨髓瘤是一种不可治愈的血液恶性肿瘤。目前，蛋白酶体抑制剂的应用在治疗这种疾病方面可能优于基于化疗的方案。然而，一些患者仍然对硼替佐米联合治疗产生耐药。因此，这项研究旨在评估这些病例中 CD69 和 CD56 的表达及其与治疗反应的关系。
对 98 例多发性骨髓瘤病例进行 4 色多参数流式细胞术免疫表型分析。通过共表达 CD38 和 CD138 与低 SSC、阴性或弱 CD45 对克隆浆细胞进行门控。
双阴性 CD69 和 CD56（47.9%）多发性骨髓瘤病例与高血清β2 微球蛋白、肌酐、钙和低血清白蛋白相关。这些标志物的缺失与溶骨性病变和不良细胞遗传学 t（4；14）（ < 0.001）之间也存在显著相关性。此外，CD69-和 CD56-在多发性骨髓瘤患者中与硼替佐米联合治疗无反应之间存在高度显著相关性（ < 0.0001）。使用不同预后指标对这些病例进行治疗无反应预测的回归分析表明，高血清β2 微球蛋白、不良细胞遗传学、晚期和 CD69 和 CD56 低表达是治疗无反应的不良预测因素。
CD69 与 CD56 联合可作为多发性骨髓瘤病例的独立预后因素。它可用于常规实验室评估，以细化分层，并为发展中国家高成本治疗及时做出治疗决策。
