Suku Pratibha, Dash Aishwarya, Radhakrishnan Aravind, Malhotra Pankaj, Sachdeva Man Updesh Singh
Department of Hematology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, P.O. Box 160012, India.
Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, P.O. Box 160012, India.
Oncol Res. 2025 Apr 18;33(5):1055-1068. doi: 10.32604/or.2024.055154. eCollection 2025.
Circulating plasma cells (CPCs) in patients of plasma cell neoplasm have been an area of intense research in recent decades. Circulating tumor plasma cells (CTPCs) might represent a sub-clone of tumor cells that have exited into peripheral blood as a result of the dynamic interactions between the bone marrow (BM) microenvironment and neoplastic plasma cells. Chemokine receptors like chemokine receptor 4 (CXCR4) and integrins are known to play a role in homing and migration of plasma cells (PCs). The hypoxic microenvironment in the BM niche also contributes to their circulation through various mechanisms. In addition, the CCL3-CCR1 axis probably competes with the retention signals from the CXCR4-α4β1 (VLA-4) interaction and actively promotes the exit of PCs from the BM. CTPCs, even in extremely low numbers, can be detected and quantified by high-sensitivity techniques like multi-color flow cytometry and next-generation sequencing. High load of CTPCs noted in patients of plasma cell neoplasm; monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), multiple myeloma (MM) is a strong predictor of shorter progression free survival (PFS) as well as overall survival (OS). In newly diagnosed patients of MM, a load of CTPCs correlates with the outcomes, i.e., OS and PFS. With more studies collaborating on the results of previous reports, assessment of the burden of CTPCs may become a complimentary approach for non-invasive risk stratification of MM patients and evaluating the response to therapy. Future research on larger cohorts and longer follow-ups may help to improve the existing staging system by incorporating the load of CTPCs as one of the prognostic indicators. Further studies based on isolation and genetic characterization of CTPCs may help in understanding the pathophysiology of the progression of the disease and may open avenues for newer treatment modalities. This review discusses the pathobiological aspects leading to circulation of neoplastic/tumor plasma cells in peripheral blood and provides a summary of research work done in last two decades on its prognostic importance in various plasma cells neoplasms.
近几十年来，浆细胞肿瘤患者的循环浆细胞（CPC）一直是深入研究的领域。循环肿瘤浆细胞（CTPC）可能代表肿瘤细胞的一个亚克隆，由于骨髓（BM）微环境与肿瘤性浆细胞之间的动态相互作用，这些肿瘤细胞已进入外周血。已知趋化因子受体如趋化因子受体4（CXCR4）和整合素在浆细胞（PC）的归巢和迁移中起作用。BM微环境中的缺氧微环境也通过各种机制促进它们的循环。此外，CCL3-CCR1轴可能与CXCR4-α4β1（VLA-4）相互作用产生的保留信号竞争，并积极促进PC从BM中逸出。即使数量极少，CTPC也可以通过多色流式细胞术和下一代测序等高灵敏度技术进行检测和定量。在浆细胞肿瘤患者中发现的高负荷CTPC；意义未明的单克隆丙种球蛋白病（MGUS）、冒烟型多发性骨髓瘤（SMM）、多发性骨髓瘤（MM）是无进展生存期（PFS）以及总生存期（OS）较短的有力预测指标。在新诊断的MM患者中，CTPC负荷与OS和PFS等预后相关。随着更多研究结合既往报道的结果，评估CTPC负荷可能成为MM患者无创风险分层和评估治疗反应的一种补充方法。未来对更大队列和更长随访时间的研究可能有助于通过将CTPC负荷纳入预后指标之一来改进现有的分期系统。基于CTPC分离和基因特征的进一步研究可能有助于理解疾病进展的病理生理学，并可能为新的治疗方式开辟道路。本综述讨论了导致肿瘤性/肿瘤浆细胞在外周血中循环的病理生物学方面，并总结了过去二十年中关于其在各种浆细胞肿瘤中的预后重要性的研究工作。
