Sourdeau Elise, Boccon-Gibod Clémentine, Corneau Aurélien, Costopoulos Myrto, Bravetti Clotilde, Armand Marine, Chapiro Elise, Nguyen-Khac Florence, Davi Frédéric, Blanc Catherine, Leblond Véronique, Baron Marine, Roos-Weil Damien, Le Garff-Tavernier Magali
Sorbonne Université, Service d'Hématologie Biologique, Hôpital Pitié-Salpêtrière APHP, Paris, France.
Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, Paris, France.
J Cell Mol Med. 2025 May;29(10):e70620. doi: 10.1111/jcmm.70620.
Waldenström Macroglobulinaemia (WM) is sometimes difficult to differentiate from marginal zone lymphoma (MZL), two entities with overlapping features for which no single marker assessed by multiparameter flow cytometry (MFC) is specific. The aim of this work was to establish a diagnostic phenotypic score for bone marrow (BM) and peripheral blood (PB) WM samples, to differentiate it from MZL and to improve the detection of small circulating WM clones. This study revealed a distinct phenotypic profile between WM and MZL B-cells. WM B-cells showed decreased expression of CD19, FMC7, CD22, CD27 and increased expression of CD79b and CD13. Supervised and unsupervised MFC analyses were used to define a phenotypic scoring system: a score of 3/6 or greater in BM or 4/7 or greater in PB samples supported the diagnosis of WM (sensitivity of 97.9% and 94.1% and specificity of 80.0% and 93.5%, respectively). These results were validated in a prospective cohort with very high sensitivity and specificity for the two scoring systems. Clinico-biological correlations showed that the absence or low expression of CD38 on BM WM B-cells was significantly associated with increased BM and PB infiltration (p < 0.0001 and p = 0.0024 respectively) and CXCR4 mutation (p < 0.0001). These results demonstrate that MFC can be used to differentiate WM from MZL with a scoring system that can be easily implemented in routine practice.
华氏巨球蛋白血症（WM）有时难以与边缘区淋巴瘤（MZL）相鉴别，这两种实体具有重叠的特征，通过多参数流式细胞术（MFC）评估的单一标志物均不具有特异性。这项工作的目的是为骨髓（BM）和外周血（PB）的WM样本建立一种诊断表型评分，以将其与MZL区分开来，并提高对小循环WM克隆的检测。这项研究揭示了WM和MZL B细胞之间不同的表型特征。WM B细胞显示CD19、FMC7、CD22、CD27表达降低，而CD79b和CD13表达增加。使用监督和非监督MFC分析来定义一种表型评分系统：BM样本中得分为3/6或更高，或PB样本中得分为4/7或更高支持WM诊断（敏感性分别为97.9%和94.1%，特异性分别为80.0%和93.5%）。这些结果在前瞻性队列中得到验证，两种评分系统均具有非常高的敏感性和特异性。临床生物学相关性显示，BM WM B细胞上CD38的缺失或低表达与BM和PB浸润增加（分别为p < 0.0001和p = 0.0024）以及CXCR4突变（p < 0.0001）显著相关。这些结果表明，MFC可用于通过一种易于在常规实践中实施的评分系统将WM与MZL区分开来。
