Biology subjects

Gunther, U. L.

Publications and source records attributed to Gunther, U. L..

2 recordsLinked to original sources

bioRxiv2021

Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells

Acute myeloid leukaemia (AML) cells interact and modulate components of their surrounding microenvironment into their own benefit. Stromal cells have been shown to support AML survival and progression through various mechanisms. Nonetheless, it is unclear whether AML cells could establish beneficial metabolic interactions with stromal cells. Here, we identify a novel metabolic crosstalk between AML and stromal cells where AML cells prompt stromal cells to secrete acetate for their own consumption to feed the tricarboxylic acid cycle (TCA). By performing transcriptome analysis, tracer-based metabolic NMR analysis and ROS measurements, we observe that stromal cells present a higher rate of glycolysis. We also find that acetate in stromal cells is derived from pyruvate via chemical conversion under the influence of reactive oxygen species (ROS) following ROS transfer from AML to stromal cells via gap junctions. Overall, we present a unique metabolic communication between AML and stromal cells that could potentially be exploited for adjuvant therapy.

cell biology↗

bioRxiv2020

Survival and Proliferation of T-cell Acute Lymphoblastic Leukaemia Depends on mTOR-regulated Glutamine Uptake and EAAT1 Activity

T-cell acute lymphoblastic leukaemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we analysed the metabolic adaptations that T-ALL cells exhibit and found that glutamine uptake is essential for their proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the TCA cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1, which is normally only expressed in the CNS, is crucial for glutamine conversion to nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment.

cancer biology↗