Metabolomic Profiling of Leukemic Hematopoiesis: Effects of BNT162b2 mRNA COVID-19 Vaccine Administration

Abstract

Background: Leukemia is marked by clonal hematopoietic stem cell expansion and metabolic reprogramming. The BNT162b2 mRNA COVID-19 vaccine has been proven effective, though questions remain about its broader physiological effects. This study investigates metabolomic alterations in leukemic bone marrow potentially associated with BNT162b2 vaccination.

Objective: To compare the bone marrow metabolomic profiles of leukemia patients with and without BNT162b2 vaccination, and healthy unvaccinated controls, to explore potential metabolic differences.

Methods: Bone marrow samples were obtained from three groups: vaccinated leukemia patients (n=7), unvaccinated leukemia patients without COVID-19 history (n=2), and unvaccinated healthy controls (n=7). Untargeted metabolomics was performed using LC-QTOF-MS. Data were analyzed using XCMS and MetaboAnalyst 5.0 to identify statistically significant metabolite differences and affected pathways. Fold change >1.5 and p<0.05 were considered significant.

Results: Distinct metabolic profiles were observed between the leukemia and control groups. Increased glycolysis, pentose phosphate pathway activity, and altered tryptophan, lipid, and heme metabolism were noted in leukemia samples. Metabolic changes in vaccinated patients (ASL) were more similar to unvaccinated leukemia patients (LO) than to healthy controls, with minor vaccine-associated variations. Notable metabolites included 5-methoxyindoleacetate, phosphorylcholine, and tetrahydrofolic acid.

Conclusion: This preliminary study identified altered metabolic pathways in leukemia bone marrow and suggests metabolomic differences associated with BNT162b2 vaccination. While the findings do not support a causal link between mRNA vaccination and leukemia development, they highlight the need for further studies to understand vaccine-induced metabolic modulation in hematological contexts.

Keywords: COVID-19; Hematopoiesis; Leukemia; Metabolomics.; SARS-CoV-2; The Pfizer-BioNTech COVID-19 vaccine.