Altered proteome of high-density lipoproteins from paediatric acute lymphoblastic leukemia survivors

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.

Dietary Intakes Are Associated with HDL-Cholesterol in Survivors of Childhood Acute Lymphoblastic Leukaemia

“…It is important to note that cALL survivors are at higher risk of developing low levels of HDL-C [8][9][10]. Alterations in HDL particle composition in lipids and proteins were also found in this population [11,12], suggesting defects in functionality. HDL particles are known for their ability to promote reverse cholesterol transport, but their functions are more extensive in view of their anti-atherosclerotic properties such as antioxidant [13,14], anti-apoptotic [15], anti-inflammatory [16], anti-hypertensive [17] and anti-thrombotic [18] roles.…”

Inflammatory Biomarkers after an Exercise Intervention in Acute Lymphoblastic Leukemia Survivors

“…Abbreviations: ADA, adenosine deaminase; ADP, adenosine diphosphate; ATP, adenosine triphosphate; BMI, body mass index; CCL, chemokine (C-C motif) ligand; CCR, C-C chemokine receptor; CSF, colony stimulating factor; CVD, cardiovascular disease; CX3CL1, chemokine (C-X3-C motif) ligand 1; CXC, C-X-C motif; CXCL, chemokine (C-X-C motif) ligand; CXCR, CXC chemokine receptor; DM, diabetes mellitus; DPP4, dipeptidyl peptidase-4; EGFR, epidermal growth factor receptor; FGF-21, broblast growth factor 21; G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte-macrophage colony stimulating factor; IL-6, interleukin-6; IR, insulin resistance, LAP TGF-β1, latency associated peptide transforming growth factor beta; MCP, monocyte chemoattractant protein; MetS, metabolic syndrome; MIP-1β, macrophage in ammatory protein-1-beta; MMP, matrix metalloproteinase; OSM, Oncostatin-M; T2DM, type 2 diabetes mellitus; TGF-α, transforming growth factor alpha; TGF-β, transforming growth factor beta; TNFSF14/LIGHT, tumor necrosis factor superfamily member 14; TRAIL/TNFSF10, tumor necrosis factor-related apoptosis-inducing ligand 10 Discussion ALL survivors did not differ in their plasma in ammatory protein levels compared to their age-and sexmatched controls. This was unexpected in light of reports of ALL survivors being at risk for in ammation [16][17][18] and accelerated aging 9 and considering the diseases a liated with these conditions, such as MetS 19 . Contrarily, this is one of the rst reports of such a result when using an in ammatory protein panel of this size.…”

Efficacy of Polyphenols in the Management of Dyslipidemia: A Focus on Clinical Studies

“…At this stage, HDL-C is removed by hepatic SR-B1, completing the reverse cholesterol transport process and ultimately ensuring that excess peripheral tissue CHOL is deposited in the liver for bile acids conversion [ 55 , 56 , 57 ]. The importance of HDL in protecting against CVD is attributed not only to its role in reverse cholesterol transport but also to its ability to act as an antioxidant, anti-inflammatory, anti-thrombotic, pro-vasodilatory and anti-apoptotic agent ( Figure 3 ) [ 38 , 58 , 59 , 60 , 61 ].…”