FIGURE 3.

Leukemic cell‐derived sEVs inhibit creatine import by CD8+ T cells. (a) Diagram showing creatine uptake and creatine‐mediated bioenergy buffering in cells. SLC6A8, solute carrier family six member eight; AGAT, glycine amidinotransferase; GAMT, guanidinoacetate methyltransferase; Cr, creatine; PCr, phospho‐creatine; Crn, creatinine; CK, creatine kinase. (b–f) CD8+ T cells were treated with NB4‐sEV, OCI/AML2‐sEV, or OCI/AML3‐sEV, and the levels of intracellular creatine (b), ATP (c), and extracellular creatine (d) are shown. The mRNA‐expression (e) and protein‐expression (f) levels of the creatine transporter SLC6A8, two enzymes controlling the de novo creatine synthesis (AGAT and GAMT), and creatine kinase (CK) were measured via qRT‐PCR and western blotting, respectively (*p < 0.05; **p < 0.01; ***p < 0.001; n.s, not significant)