Syndrome métabolique affectant les survivants de la leucémie lymphoblastique aiguë pédiatrique : rôle et dysfonctions des lipoprotéines « HDL »
Acute lymphoblastic leukemia is the most frequent malignancy in children. With the use of more modern, efficient treatments, 5-year survival has reached more than 90% in this population. However, this achievement comes with many long-term effects: more than 65% of the survivors experience at least one severe complication, including the metabolic syndrome and cardiovascular diseases. In this context, a significant proportion of pediatric cancer survivors have low HDL-Cholesterol levels. The causes of such an abnormality remain so far unknown. HDLs are multifunctional particles, which are primordial in maintaining cardiovascular health given their antioxidative, anti-atherosclerosis, anti-inflammatory and anti- thrombotic capacities, to name but a few functions. Accordingly, studies on HDL functionality in diverse pathologies have revealed some important losses of functions linked to an altered composition. The main objective of the present work was to characterize the composition and functionality of HDLs isolated from pediatric acute lymphoblastic leukemia survivors. The HDL fractions from the survivors contained less cholesterol than the controls. In addition, proteomic analyses using mass spectrometry revealed an enrichment of pro-thrombotic (e.g. fibrinogen) and pro-inflammatory (e.g. serum amyloid A) proteins in the HDLs deriving from metabolically unhealthy survivors. The cholesterol efflux and antioxidant capacities of these HDLs were similar to those of the controls. These results indicate an alteration in the composition of lipid and protein content of HDLs from childhood acute lymphoblastic leukemia survivors with metabolic disorders. Although more work is needed to validate the functionality of these HDLs, the data seem relevant for survivor health given the detection of potential biomarkers related to HDL metabolism and functionality in cancer.
HDL Lipoproteins Cancer survivors Metabolic syndrome Proteomics