For the first time, it has been shown that, small extracellular vesicles from T-ALL leukemia cells remodel the vascular microenvironment and suppress normal hematopoiesis by activating the protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 (eIF2)/activating transcription factor 4 (ATF4)/jagged1 (JAG1) axis in ECs. Here, EIF2AK3 is linked to acute lymphoblastic leukemia.