Zhang Haotian, Castiglione Melissa, Zheng Lei, Zhan Huichun
Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY, USA.
Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY, USA.
Exp Hematol Oncol. 2021 Oct 19;10(1):47. doi: 10.1186/s40164-021-00241-2.
Disease relapse after allogeneic stem cell transplantation is a major cause of treatment-related morbidity and mortality in patients with myeloproliferative neoplasms (MPNs). The cellular and molecular mechanisms for MPN relapse are not well understood. Here, we established a murine model of MPN relapse, in which ~ 60% of the MPN recipient mice develop disease relapse after receiving stem cell transplantation with wild-type marrow donor. Using this model, we find that impaired wild-type cell function is associated with MPN disease relapse. We also show that competition between wild-type and JAK2V617F mutant cells can modulate the immune cell composition and PD-L1 expression induced by the JAK2V617F oncogene. These results suggest that cell competition between wild-type donor cells and JAK2V617F mutant recipient cells can prevent MPN disease relapse after stem cell transplantation.
异基因干细胞移植后疾病复发是骨髓增殖性肿瘤(MPN)患者治疗相关发病和死亡的主要原因。MPN复发的细胞和分子机制尚未完全明确。在此,我们建立了一个MPN复发的小鼠模型,其中约60%的MPN受体小鼠在接受野生型骨髓供体的干细胞移植后发生疾病复发。利用该模型,我们发现野生型细胞功能受损与MPN疾病复发相关。我们还表明,野生型细胞与JAK2V617F突变细胞之间的竞争可以调节由JAK2V617F致癌基因诱导的免疫细胞组成和PD-L1表达。这些结果表明,野生型供体细胞与JAK2V617F突变受体细胞之间的细胞竞争可以预防干细胞移植后MPN疾病的复发。