Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
Department of Pediatric Oncology and Hematology, Medical University of Bialystok, Bialystok, Poland.
Front Immunol. 2024 Sep 25;15:1446687. doi: 10.3389/fimmu.2024.1446687. eCollection 2024.
Acute lymphoblastic leukemia is characterized by a disturbed maturation of hematopoietic stem cells (HSCs) resulting in development of a malignant clone. Despite relatively positive outcome, there are still instances of disease relapse occurring due to ineffective disease eradication or primary leukemic clone alterations. Unclear significance of stem cells in the course of ALL led us to investigate and establish crucial changes in two stem cell populations - very small embryonic-like stem cells (VSELs) and HSCs during the induction phase of treatment.
In a retrospective study selected stem cells in peripheral blood and bone marrow of 60 pediatric ALL subjects and 48 healthy controls were subjected to flow cytometric analysis at 4 different time points.
Both VSELs and HSCs were elevated at the moment of ALL diagnosis compared to healthy controls, but profoundly decline until day 15. Further observations revealed an increase in HSCs with a concomitant depletion of VSELs until week 12. ALL patients with high HSCs showed positive correlation with bone marrow blasts at diagnosis. Patients with lower VSELs or HSCs at diagnosis had slightly improved response to applied therapy. We observed higher initial bone marrow lymphoblast values in patients with lower VSELs or higher HSCs in the high-risk group. The significance of VSELs in predicting treatment outcome can be illustrated by lower day 15 MRD level of patients with lower VSELs at diagnosis.
We found HSCs and VSELs to be valid participants in pediatric ALL with possible contribution in the neoplastic process and prediction of initial treatment outcome.
急性淋巴细胞白血病的特征是造血干细胞（HSCs）的成熟过程紊乱，导致恶性克隆的发展。尽管治疗结果相对较好，但由于疾病清除不彻底或白血病克隆的改变，仍有疾病复发的情况发生。由于急性淋巴细胞白血病（ALL）中干细胞的意义不明确，我们研究并确定了治疗诱导期两个干细胞群体——非常小的胚胎样干细胞（VSELs）和 HSCs 的关键变化。
在一项回顾性研究中，我们选择了 60 名儿科 ALL 患者和 48 名健康对照者的外周血和骨髓中的干细胞，并在 4 个不同时间点进行流式细胞术分析。
与健康对照组相比，ALL 诊断时 VSELs 和 HSCs 均升高，但在第 15 天明显下降。进一步观察发现，HSCs 增加，同时 VSELs 减少，直到第 12 周。ALL 患者中 HSCs 高的患者与诊断时骨髓原始细胞呈正相关。诊断时 VSELs 或 HSCs 较低的患者对应用治疗的反应略有改善。我们观察到高危组中 VSELs 较低或 HSCs 较高的患者初始骨髓淋巴母细胞值较高。VSELs 对预测治疗结果的意义可通过较低的第 15 天 MRD 水平来体现，即诊断时 VSELs 较低的患者。
我们发现 HSCs 和 VSELs 是儿科 ALL 的有效参与者，可能有助于肿瘤发生过程，并预测初始治疗结果。
