Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has a dismal
prognosis. Ιt was found that T cells of patients relapsing with AML after allo-HCT exhibited reduced glycolysis and
interferon-γ production. Functional studies in multiple mouse models of leukemia showed that leukemia-derived
lactic acid (LA) interfered with T cell glycolysis and proliferation. Mechanistically, LA reduced intracellular pH
in T cells, led to lower transcription of glycolysis-related enzymes, and decreased activity of essential metabolic
pathways. Metabolic reprogramming by sodium bicarbonate (NaBi) reversed the LA-induced low intracellular pH,
restored metabolite concentrations, led to incorporation of LA into the tricarboxylic acid cycle as an additional
energy source, and enhanced graft-versus-leukemia activity of murine and human T cells. NaBi treatment of post–
allo-HCT patients with relapsed AML improved metabolic fitness and interferon-γ production in T cells. Overall, metabolic reprogramming of donor T cells is a pharmacological strategy for patients with relapsed
AML after allo-HCT.

Presenter:Prof.Spyridonidis
Participants:Dr Liga, Dr Tsokanas