Metabolic Alterations and Elevation of Oxidative Stress during the Early Post-Transplant Period in AML Patients

Introduction

Metabolic reprogramming as one of the hallmarks of cancer is necessary to satisfy the increased cell demands for energy and biosynthetic precursors. Our earlier study showed that the concentrations of TCA cycle, glycolysis metabolites, and oxidative stress markers differ significantly among individual stages of AML patient treatment before transplantation, but do not reach the values of healthy metabolism. In this work, we focused on pre-transplant (conditioning regimens) and early post-transplant periods in AML patients, specifically we monitored changes in concentrations of proteinogenic amino acids, metabolites of basic metabolic pathways, and oxidative stress markers.

The aim of this study was to characterize concentration profiles of selected metabolites and oxidative stress markers during pre-transplant and early post-transplant periods and to reveal their possible influence on post-transplantation development.

Methods

Metabolomic profiles were generated using serum samples obtained at pre- and post-transplantation from selected patients treated in the Institute of Hematology and Blood Transfusion, Prague, Czech Republic. Targeted metabolomic profiling of selected metabolites related mainly to TCA cycle, glycolysis, proteinogenic amino acid, and markers of oxidative stress was performed by LC-MS/MS.

Results

Using non-parametric Wilcoxon test we found a significant decrease in most of the quantified metabolites of the citrate cycle and glycolysis during conditioning regimens. Conversely, in the case of proteinogenic amino acids, we found significant changes in 14 proteinogenic amino acids, specifically in 12 of them there was a significant increase during the conditioning regimens. To assess oxidative stress, we quantified total malondialdehyde as a marker of lipoperoxidation and pyroglutamate as a marker of glutathione depletion. We found that during conditioning regimens, there was a significant increase in malondialdehyde and a simultaneous increase in pyroglutamate. Moreover, we found that oxidative stress presented by malondialdehyde concentration significantly increased 7, 14, and 21 days after transplantation in comparison to the state before conditioning regimens. The lowest decrease in concentrations of TCA cycle and glycolysis metabolites occurred around day 7 post-transplantation. The suppression of monitored metabolic pathways resolved after 21 days post-transplantation.

Conclusion The results of our preliminary targeted metabolomic profiling of AML patients contribute to expanding the knowledge of metabolite concentrations and their changes during pre/post-transplantation. Together with the description of the level of oxidative stress, it may reveal a possible influence on development after transplantation and could have a potential impact on supportive treatment regimens even after transplantation.

Acknowledgement This work was supported by the European Regional Development Fund and the state budget of the Czech Republic (project AIIHHP: CZ.02.1.01/0.0/0.0/16_025/0007428, OP RDE, Ministry of Education, Youth and Sports) and by the project of the Ministry of Health, Czech Republic (00023736).

No relevant conflicts of interest to declare.