Induction chemotherapy reduces extracellular heat shock protein 72 levels, inflammation, lipoperoxidation and changes insulin sensitivity in children and adolescents newly diagnosed with acute lymphoblastic leukemia

Oncotarget. 2018 Jun 19;9(47):28784-28795. doi: 10.18632/oncotarget.25609.

Abstract

Background: Acute lymphoblastic leukemia (ALL) is associated with higher levels of pro-inflammatory cytokines and oxidative stress. Recently, the levels of extracellular heat shock protein 72 (eHSP72) were found to be elevated in ALL, and its elevation associated with poor prognosis. Therefore, considering the possible role of eHSP72 as a modulator of the immunological system and metabolism, the aim of this study was to describe the response of eHSP72 to the induction phase of chemotherapy, along with metabolic, inflammatory and oxidative stress markers, in children and adolescents newly diagnosed with ALL.

Methods: Nineteen patients were recruited and analysed before and after the induction phase of chemotherapy (with 28 days of duration). Blood samples were taken for the analysis of C-reactive protein (CRP), levels of lipoperoxidation, insulin (and HOMA-IR), cortisol, glucose, lipid profile and eHSP72.

Results: We found that induction phase of chemotherapy leads to a drop in glucose levels (from 101.79±19 to 75.8±9.7 mg/dL), improvements on inflammation (CRP levels, p<0.01) and oxidative stress (TBARS levels, p<0.01), reduction on eHSP72 (p=0.03) and improved insulin sensitivity (HOMA-IR, p=0.02).

Conclusion: Our results indicate that eHSP72 may have an immune and metabolic role and could be used as a marker of the treatment success and metabolic changes in children with ALL.

Keywords: acute lymphoblastic leukemia; chemotherapy; eHSP72; glycaemia and inflammation; oxidative stress.