12/15-LOX maintains the number of LT-HSC. (A) Kaplan-Meier plot of secondary recipients of B6 and Alox15 BM. BM cells from lethally irradiated primary recipients were harvested 16 weeks after engraftment of B6 and Alox15 BM cells and transferred into secondary lethally irradiated congenic recipients, and survival was monitored (n = 5). (B) Neutrophils in the blood of secondary recipients at 15 weeks after secondary reconstitution compared with mice with MPD eliminating MPD as the cause of morbidity in Alox15 secondary recipients. (C) Increased ratio of MP (Lin⁻Sca1⁻cKit⁺) to LSK and CLP to LSK quantified by flow cytometry day 4 after treatment with 200 mg/kg 5-FU indicate a defect in maintenance of LSK numbers in Alox15 mice compared with B6 (n = 9). (D-E) Kinetics of expansion of LSK and progenitor populations in 5-FU–treated B6 and Alox15 mice, demonstrating loss of the LSK subset in Alox15 mice by day 8. (D) Number of LSK, MP, and CLP in Alox15 mice after treatment with 5-FU. (E) Representative flow cytometric analyses at times indicated of gated Lin⁻ cells with percentage of progenitor and LSK subsets among total cells shown. (F) Kaplan-Meier plot demonstrating decreased survival of 5-FU–treated Alox15 mice compared with B6 (n = 8).