Subversion of Serotonin Receptor Signaling in Osteoblasts by Kynurenine Drives Acute Myeloid Leukemia.
Marta Galán-DíezFlorence BorotAbdullah Mahmood AliJunfei ZhaoEva Gil IturbeXiaochuan ShanNa LuoYongfeng LiuXi-Ping HuangBrygida BisikirskaRossella LabellaIrwin KurlandBryan L RothMatthias QuickSiddhartha MukherjeeRaul RabadánMartin CarrollAzra RazaStavroula KousteniPublished in: Cancer discovery (2022)
AML remains recalcitrant to treatments due to the emergence of resistant clones. We show a leukemia-cell nonautonomous progression mechanism that involves activation of a kynurenine-HTR1B-SAA-IDO1 axis between AML cells and osteoblasts. Targeting the niche by interrupting this axis can be pharmacologically harnessed to hamper AML progression and overcome therapy resistance. This article is highlighted in the In This Issue feature, p. 873.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- induced apoptosis
- cell cycle arrest
- single cell
- cell therapy
- machine learning
- deep learning
- cancer therapy
- signaling pathway
- stem cells
- oxidative stress
- drug delivery
- acute lymphoblastic leukemia
- endoplasmic reticulum stress
- cell death
- neural network
- smoking cessation