CD43 expression is an adverse prognostic factor in newly diagnosed multiple myeloma Introduction CD43 is an abundant, heavily-glycosylated, cell surface protein expressed on bone marrow hematopoietic stem cells and most white blood cells. Previous studies have found that CD43 also expressed in some types of lymphoma cells and associated with adverse outcomes. However, the prognosis value of CD43 expression in multiple myeloma (MM) remain unknown. Patients and Methods A total of 109 MM patients, newly diagnosed in Nanfang Hospital of Southern Medical University from January 2017 to December 2019, were included in the study. CD43 was detected by flow cytometre as follows: 2 ml of heparin anticoagulated bone marrow was collected from the patients at the time of diagnosis,1×10 6 cells were detected, and a gate was set for identifying abnormal plasma cells characterized by CD138 expression and CD38. CD43 positive was defined as more than 20% of the plasma cells expressed CD43. Results A total of 109 patients with newly diagnosed MM were enrolled in the study, including 77 patients (70.6%) for CD43 positive and 32 patients (29.4%) for CD43 negative . The median age was 58 years, and the male-female ratio was 1.7:1. Patients in the CD43 positive group were more likely to have international staging system (ISS) stage III (67.5% VS 46.9%, P= 0.044), hemoglobin < 85g/L (64.9% VS 37.5%, P= 0.008), 13q deletion (31.4% VS 10.4%), and higher percentage of bone marrow monoclonal plasma cells detected by flow cytometry (5.5% VS 1.4%, P=0.003). Most patients enrolled in the study received bortezomib-based treatment. The very good partial response (VGPR) or better rate after 4 induction cycles was significantly lower in the CD43 positive group than CD43 negative group (35.1% VS 56.3%, P=0.041), and the overall response rate (ORR) in the CD43 positive group was lower than that in CD43 negative group (75.3% VS 84.4%, P=0.299), but no significantly difference. The median follow-up time was 22 months. Patients with CD43 positive had significantly lower PFS (median PFS 24 months VS not reached, P =0.012), and OS (median OS not reached, P = 0.023) than those with CD43 negative. Multivariate analysis indicated that CD43 positive expression was an independent poor risk factor for PFS (HR 2.517 95%CI 1.178-5.376, P = 0.017) and OS (HR 3.664 95%CI 1.100-12.075, P = 0.034). Conclusion Our study showed that CD43 expression was an adverse prognosis for multiple myeloma. Disclosures No relevant conflicts of interest to declare.
CD44 expression in different plasma cell diseases Introduction Myeloma is a genetically complex disease which develops via a multistep process whereby plasma cells are driven towards malignancy through the accumulation of genetic "hits" over time. This multistep process permits myeloma to have four recognisable clinical stages including monoclonal gammopathy of undetermined significance (MGUS) , smouldering multiple myeloma (SMM) , multiple myeloma (MM) and plasma cell leukemia (PCL). CD44 as a complex adhesion molecule, is highly expressed in a variety of solid tumors and involved in metastasis and chemotherapy resistance . Previous studies had found that CD44 was also highly expressed in MM, and associated with advanced clinical stage, extramedullary myeloma (EM) and poor survival. However the relation of CD44 expression in different plasma cell disease remain unknown. Patients and Methods Newly diagnosed MGUS (n=12), SMM (n=11), MM (n=133) and PCL (n = 8) patients who were hospitalized in our hospital from December 2017 to December 2020 were enrolled. The diagnosis was based on the criteria of the International Myeloma Working Group. CD44 was detected by flow cytometry as follows: 2 ml of heparin anticoagulated bone marrow was collected from the patients at the time of diagnosis, 1×10 6 cells were detected, and a gate was set for identifying abnormal plasma cells characterized by CD138 and CD38. CD44 positive was defined as more than 20% of the plasma cells expressed CD44. Results From December 2017 to December 2020, a total of 164 patients diagnosed in our hospital were included in the study, including 12 MGUS patients, 11 SMM patients, 133 MM patients and 8 PCL patients. The expression proportion (7.9%±11.9%, 11.2%±15.5%, 40.2%±37.7%, 81.9%±25.6%, P < 0.001) and expression intensity (the mean fluorescence intensity was 1 742.8±1 023.1, 2 915.7±923.0, 6 692.6±11 275.5, 25 359.6±22 604.5, P=0.001) of CD44 on the monoclonal plasma cells of MGUS, SMM, MM and PCL patients gradually increased. In 133 MM patients, 73 cases were for CD44 positive. CD44 positive patients were more likely to show >3 focal bone lesion (75.3% VS 50.0%, P=0.002), and international staging system(ISS)III stage (68.5% VS 51.7%, P=0.048) compared those with CD44 negative. CD44 expression rate was significantly higher in MM patients with extramedullary disease (n=26) than those without (n=107) (56.7%VS 36.2%, P=0.031) Conclusion: Our study showed that from MGUS, SMM, MM to PCL, the CD44 expression on abnormal plasma cells was gradually increased. CD44 overexpression was associated with osteolytic lesions, advanced ISS staging and extramedullary myeloma. The results indicated that CD44 was related to the invasion degree of plasma cell disease, and could be used as a marker for differential diagnosis between different plasma cell disease. Disclosures No relevant conflicts of interest to declare.
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