Abstract
Acute lymphoblastic leukemia (ALL) 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 secondary and long-term effects since more than 65% of the survivors experience at least one severe complication, including the metabolic syndrome and cardiovascular diseases. The main objective of the present work was to characterize the composition of HDL particles isolated from pediatric ALL survivors. HDLs from 8 metabolically healthy ALL survivors, 8 metabolically unhealthy ALL survivors and 8 age- and gender-matched controls were analyzed. The HDL fraction from the survivors contained less cholesterol than the controls. In addition, proteomic analyses revealed an enrichment of pro-thrombotic (e.g., fibrinogen) and pro-inflammatory (e.g., amyloid A) proteins in the HDLs deriving from metabolically unhealthy survivors. These results indicate an alteration in the composition of lipid and protein content of HDL from childhood ALL 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.
Highlights
Childhood cancers are rare, representing only 0.5–1% of all the cancers diagnosed in Canada
The present study includes a total of 24 subjects (50% males): 8 healthy subjects (Controls), 8 metabolically healthy Acute lymphoblastic leukemia (ALL) survivors (Healthy), and 8 metabolically unhealthy ALL survivors (Unhealthy)
At least one Unhealthy was treated under a version of every protocol
Summary
Childhood cancers are rare, representing only 0.5–1% of all the cancers diagnosed in Canada. HDL particles are widely known in view of their anti-atherosclerotic properties These features are due to their ability to promote reverse cholesterol transport[11], but are likely the result of many functions, which help maintain metabolic health because of their antioxidant[12,13], anti-apoptotic, anti-inflammatory[14,15,16], anti-hypertensive[17,18] and anti-thrombotic[19] capacities. These numerous functions are made possible by the large variety of protein and lipid moieties within the HDL fraction. Our objective was to describe the global HDL composition and further investigate the changes in the proteome of HDLs isolated from childhood ALL survivors
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