Yang Suwen, Hu Qianwen, Wang Xiaofen, Qiao Sai, Qi Chao, Jin Hong, Zhong Yuhong
Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, China.
Int J Lab Hematol. 2025 Feb;47(1):110-119. doi: 10.1111/ijlh.14366. Epub 2024 Sep 12.
Anti-CD38 therapeutic modalities (e.g., daratumumab) can impede classical CD38 and CD138 gating use for plasma cell (PC) detection in multiple myeloma (MM) patients with minimal residual disease (MRD). We assessed the applicability of CD229, CD269, and interferon regulatory factor (IRF-4) for PC detection in MM MRD patients.
Bone marrow samples were collected from patients with MM. Through multiparameter flow cytometry, we evaluated the suitability of CD229, CD269, and IRF-4 for distinguishing PCs from other hematopoietic cells and compared their expression pattern on normal PCs (nPCs) and aberrant PCs (aPCs). We also assessed IRF-4 expression stability after sample storage under different conditions. A 10-color MRD antibody panel was used to determine whether IRF-4 is an alternative primary PC-gating marker for MM MRD assessment.
IRF-4 was expressed specifically on all PCs; its mean fluorescence intensity (MFI) was highest on PCs among all hematopoietic cells. This MFI did not decrease even after sample storage at 4°C or 25°C for 72 h. In all 42 MRD assessment samples, except for samples (n = 10) with no PCs, the use of IRF-4 enabled accurate nPC (n = 12), aPC (n = 13), and nPC + aPC (n = 7) identification. Even samples from daratumumab-treated patients had high IRF-4 MFI, with no difference between pre-treatment and post-treatment (n = 7; p = 0.610).
IRF-4 demonstrates high MFI on PCs, and it is not expressed on other leukocytes. In MM patients with MRD, daratumumab treatment does not affect IRF-4 expression. IRF-4 is a promising marker for PC identification in MRD assessment of MM patients undergoing anti-CD38 therapy.
抗CD38治疗方式（如达雷妥尤单抗）会妨碍在微小残留病（MRD）的多发性骨髓瘤（MM）患者中使用经典的CD38和CD138门控来检测浆细胞（PC）。我们评估了CD229、CD269和干扰素调节因子（IRF-4）在MM MRD患者中用于检测PC的适用性。
采集MM患者的骨髓样本。通过多参数流式细胞术，我们评估了CD229、CD269和IRF-4用于区分PC与其他造血细胞的适用性，并比较了它们在正常PC（nPC）和异常PC（aPC）上的表达模式。我们还评估了在不同条件下样本储存后IRF-4的表达稳定性。使用10色MRD抗体组合来确定IRF-4是否是用于MM MRD评估的替代原发性PC门控标志物。
IRF-4在所有PC上特异性表达；其平均荧光强度（MFI）在所有造血细胞中的PC上最高。即使样本在4°C或25°C储存72小时后，该MFI也没有降低。在所有42个MRD评估样本中，除了没有PC的样本（n = 10）外，使用IRF-4能够准确识别nPC（n = 12）、aPC（n = 13）和nPC + aPC（n = 7）。即使是来自接受达雷妥尤单抗治疗患者的样本也有较高的IRF-4 MFI，治疗前和治疗后之间没有差异（n = 7；p = 0.610）。
IRF-4在PC上表现出高MFI，并且在其他白细胞上不表达。在患有MRD的MM患者中，达雷妥尤单抗治疗不影响IRF-4的表达。IRF-4是在接受抗CD38治疗的MM患者的MRD评估中用于识别PC的有前景的标志物。
