LAUSR

B cell precursor acute lymphoblastic leukemia (BCP ALL), the most common childhood cancer, is a malignant disorder that originates from the lymphoid precursor cells committed to B-cell lineage in the bone marrow. Although genetic abnormalities disturb the normal maturation process of these lymphoid precursor cells resulting in the formation of leukemia cells and suppression of normal hematopoiesis, environmental factors seem to modulate disease progression. The underline mechanism is not clear yet. In this study, we hypothesize environmental pollutants-AHR and small molecule chaperone-WLS are involved in promoting the oncogenic effect and disease relapse of BCP-ALL leukemia cells and inhibiting normal hematopoietic function. Here, we show that Indeno [1,2,3-cd] pyrene (IP) promotes oncogenic activities in vitro and in vivo. Mechanistically, IP treatment activates AHR-IDOs axis to enhance tryptophan metabolism and bioactive metabolite- kynurenine (kyn) level, further promoting kyn-AHR signal enhanced loop. In orthotopic xenograft mouse model, IP treatment decreases disease relapse time and increases cell population of BCP ALL. These results show PAH (IP) exposure promotes the disease progression of BCP ALL. Citation Format: Li-Ting Wang, Shih-Hsien Hsu. AHR-WLS complex correlates with poor prognosis in B-cell precursor acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2587.