Significance of CD229 expression assessment for detection of minimal residual disease in patients with multiple myeloma.

Abstract Introduction Multiparameter flow cytometry (MFC) is one of the most reliable methods for monitoring minimal residual disease (MRD) in patients with multiple myeloma (MM), based on simultaneous evaluation of many immunophenotypic characteristics of plasma cells (PCs). However, the presence of normal polyclonal PCs in the sample makes it difficult to detect the residual clone using MFC. Furthermore, the monoclonal antibodies (mAbs) that are included in the treatment regimens, i.e. anti-CD38 mAbs, complicate the use of the main MRD gating strategies. Therefore, it is necessary to find new informative markers to perform a high-sensitivity MRD assessment. In this regard, CD229 is of interest but its application is insufficiently studied (Rai et al. IJLH 2023). Methods We analyzed 43 bone marrow samples obtained from 35 patients with MM: prior to the autologous stem cell transplantation (ASCT) (n = 20) and in the post-ASCT (n = 17). MRD was quantified using the 10-color flow cytometry with the analysis sensitivity of 10–5. The diagnostic panel of monoclonal antibodies was extended to include CD229, for which both the number of cells positive for the expression and normalized mean fluorescence intensity (MFI) values were assessed. Normalized MFI was calculated by dividing CD229 MFI of PCs to the CD229 MFI of monocytes in the same sample. Results Based on the results obtained, CD229 is expressed in all PCs of the studied polyclonal (n = 35) and monoclonal (n = 30) populations and in all cases (n = 12) when the monoclonal CD38-antobodies were used for the treatment. The CD229 MFI value for the abnormal PCs is 6.48 (Q1 – Q3: 3.70 – 10.80) and exceeds (p = 0.006) that for the normal PCs (3.40, Q1 – Q3: 2.82 – 4.51). Conclusions Statistically significant differences identified in the CD229 expression for the normal and abnormal PCs can be used in the MRD assessment as an additional diagnostic criterion. Our data confirm that CD229 is a reliable marker even when the expression of other commonly analyzed antigens is altered due to the effects of therapeutic mAbs. Therefore, CD229 is particularly valuable in the context of modern immunotherapeutic approaches to multiple myeloma.