肿瘤衍生因子被认为可以调节癌症患者的血小板增多症和红细胞减少症。然而，这些因素尚未确定。在这里，我们发现肿瘤细胞释放的犬尿氨酸（Kyn）通过激活芳基烃受体-Runt相关转录因子1（AhR-RUNX1）轴，使癌症个体的巨核细胞-红系祖细胞（MEP）分化为巨核细胞。在肿瘤生长过程中，肿瘤细胞中的大量 Kyn 被释放到外周，在那里它们被 MEP 通过转运蛋白 SLC7A8 吸收。在细胞质中，Kyn 结合并激活 AhR，导致其易位到细胞核中，AhR 反式激活 RUNX1，从而调节 MEP 分化为巨核细胞。此外，激活的 AhR 上调 MEP 中的 SLC7A8，从而诱导正反馈。重要的是，Kyn-AhR-RUNX1 调节的 MEP 分化在人源化小鼠和癌症个体中得到证实，为预防血小板增多症和红细胞减少症提供了潜在策略。© 2023。作者。

Tumor-derived factors are thought to regulate thrombocytosis and erythrocytopenia in individuals with cancer; however, such factors have not yet been identified. Here we show that tumor cell-released kynurenine (Kyn) biases megakaryocytic-erythroid progenitor cell (MEP) differentiation into megakaryocytes in individuals with cancer by activating the aryl hydrocarbon receptor-Runt-related transcription factor 1 (AhR-RUNX1) axis. During tumor growth, large amounts of Kyn from tumor cells are released into the periphery, where they are taken up by MEPs via the transporter SLC7A8. In the cytosol, Kyn binds to and activates AhR, leading to its translocation into the nucleus where AhR transactivates RUNX1, thus regulating MEP differentiation into megakaryocytes. In addition, activated AhR upregulates SLC7A8 in MEPs to induce positive feedback. Importantly, Kyn-AhR-RUNX1-regulated MEP differentiation was demonstrated in both humanized mice and individuals with cancer, providing potential strategies for the prevention of thrombocytosis and erythrocytopenia.© 2023. The Author(s).