Ultra-high-dose-rate FLASH radiation therapy has been shown to minimize side effects of irradiation in various organs while keeping antitumor efficacy. This property, called the FLASH effect, has caused enthusiasm in the radiation oncology community because it opens opportunities for safe dose escalation and improved radiation therapy outcome. Here, we investigated the impact of ultra-high-dose-rate FLASH versus conventional-dose-rate (CONV) total body irradiation (TBI) on humanized models of T-cell acute lymphoblastic leukemia (T-ALL) and normal human hematopoiesis.

Highlights d Hypoxia favors human lymphoid development from early hemato-lymphoid progenitors d HIF-1/2a factors enhance the lymphoid gene expression program of LMPP and pro-T/NK cells d HIF-1/2a factors are required for lymphoid cell production from LMPP and pro-T/NK cells