Subversion of serotonin-receptor signaling in osteoblasts by kynurenine drives Acute Myeloid Leukemia
Cancer Discovery, Jan 19, 2022
Marta Galan-Diez, Florence Borot, Abdullah Mahmood Ali, Junfei Zhao, Eva Gil-Iturbe, Xiaochuan Shan, Na Luo, Yongfeng Liu, Xi-Ping Huang, Brygida Bisikirska, Rossella Labella, Irwin Kurland, Bryan L Roth, Matthias Quick, Siddhartha Mukherjee, Raul Rabadan, Martin Carroll, Azra Raza, Stavroula Kousteni
In this study, Authors highlight the role of the bone marrow niche in the pathogenesis, maintenance and resistance to treatment of hematologic malignancies through both the Kynurenine and Serotonin pathways. In particular, Kynurenine secreted by Acute Myeloid Leukemia (AML) promotes, via the activation of 5HTR1B expressed in osteoblasts, a pro-inflammatory state associated with the production of Serum Amyloid A (SAA), which in turns entertains IDO1 expression and activity thereby promoting AML progression. This outstanding work underlines a new KYN–5HTR1B–SAA– IDO axis participating in AML progression and figures as an innovative therapeutic target. In this study, Tryptophan and Kynurenine levels were measured in plasma samples using ImmuSmol ELISA kits (# ISE-2227).