Metabolic Profiling as an Approach to Differentiate T-Cell Acute Lymphoblastic Leukemia Cell Lines Belonging to the Same Genetic Subgroup

Author:

Alabed Husam B. R.1ORCID,Pellegrino Roberto Maria1ORCID,Buratta Sandra12,Lema Fernandez Anair Graciela3ORCID,La Starza Roberta3ORCID,Urbanelli Lorena12ORCID,Mecucci Cristina3,Emiliani Carla12,Gorello Paolo12ORCID

Affiliation:

1. Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy

2. Centro di Eccellenza sui Materiali Innovativi Nanostrutturati (CEMIN), University of Perugia, Via del Giochetto, 06123 Perugia, Italy

3. Hematology and Bone Marrow Transplantation Unit, Laboratory of Molecular Medicine (CREO), Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive tumor mainly affecting children and adolescents. It is driven by multiple genetic mutations that together define the leukemic phenotype. Interestingly, based on genetic alterations and/or deregulated expression, at least six genetic subgroups have been recognized. The TAL/LMO subgroup is one of the most represented genetic subgroups, characterizing 30–45% of pediatric T-ALL cases. The study of lipid and metabolic profiles is increasingly recognized as a valuable tool for comprehending the development and progression of tumors. In this study, metabolic and lipidomic analysis via LC/MS have been carried out on four T-ALL cell lines belonging to the TAL/LMO subgroup (Jurkat, Molt-4, Molt-16, and CCRF-CEM) to identify new potential metabolic biomarkers and to provide a subclassification of T-ALL cell lines belonging to the same subgroup. A total of 343 metabolites were annotated, including 126 polar metabolites and 217 lipid molecules. The statistical analysis, for both metabolic and lipid profiles, shows significant differences and similarities among the four cell lines. The Molt-4 cell line is the most distant cell line and CCRF-CEM shows a high activity in specific pathways when compared to the other cell lines, while Molt-16 and Jurkat show a similar metabolic profile. Additionally, this study highlighted the pathways that differ in each cell line and the possible enzymes involved using bioinformatic tools, capable of predicting the pathways involved by studying the differences in the metabolic profiles. This experiment offers an approach to differentiate T-ALL cell lines and could open the way to verify and confirm the obtained results directly in patients.

Funder

European Union

Publisher

MDPI AG

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