Harvard-MIT Department of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Boston, MA, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Commun Biol. 2024 Apr 20;7(1):483. doi: 10.1038/s42003-024-06181-x.
Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of CLC dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1-2 orders of magnitude longer than solid tumor circulating tumor cells. We further observe that: (i) leukemia presence in the marrow can limit the clearance of CLCs in a model of acute lymphocytic leukemia (ALL), and (ii) CLCs in a model of relapsed acute myeloid leukemia (AML) can clear faster than their untreated counterparts. Our approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance. Our research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells.
白血病及其骨髓微环境在疾病过程中会发生动态变化。然而，人们对白血病细胞的循环动力学知之甚少，也不知道特定因素对清除血液中循环白血病细胞（CLCs）的影响。为了基本了解疾病进展和治疗反应过程中 CLC 的动力学，我们在急性白血病的小鼠模型中应用了血液交换方法。我们发现 CLC 在血液中循环的时间比实体肿瘤循环肿瘤细胞长 1-2 个数量级。我们进一步观察到：（i）骨髓中白血病的存在会限制急性淋巴细胞白血病（ALL）模型中 CLC 的清除，（ii）复发急性髓系白血病（AML）模型中的 CLC 比未治疗的 CLC 清除速度更快。我们的方法还可以直接定量微环境因素对 CLC 清除特性的影响。例如，来自两种白血病模型的数据表明，血管黏附分子 E-选择素会改变 CLC 的清除。我们的研究强调了 CLC 的清除率可能会因肿瘤和治疗状态而变化，并提供了一种识别控制循环细胞动力学的基本过程和因素的策略。
