Serum heat shock protein 90 as a future predictive biomarker in childhood acute lymphoblastic leukemia

Abstract

Heat shock proteins (HSPs) attract the attention of scientists and clinicians due to their potential role as diagnostic and prognostic factors in a variety of cancers. HSP90 is one of the most important and well-known family members, necessary for maintaining intracellular homeostasis. In the extracellular space, it is responsible for the transmission of alarm signals to the immune system. Numerous reports have indicated that the level of intra - and extracellular HSP90 can correlate either with a poorer prognosis or with a better outcome, depending on the type of cancer. Still, little is known why the level of this chaperone is increased in some tumors and decreased in others, reflecting dual role of protein in cell death processes. Currently, there is no database reporting levels of serum HSP90 in children with acute lymphoblastic leukemia (ALL). As such, using enzyme-linked immunosorbent assay (ELISA) method, we aimed to determine this parameter in a group of 21 patients with newly diagnosed ALL. We found decreased protein serum levels in patients at disease presentation and after induction block of chemotherapy in comparison to healthy controls. Furthermore, we observed a negative correlation between HSP90 serum levels and one of the earliest prognostic factors of the treatment response – peripheral blood lymphoblasts on the 8 th day of treatment. Our results indicate that HSP90 serum may play an important role in leukemogenesis and could be used as a marker to predict treatment failure in children with ALL.

Association between Serum Heat Shock Proteins and Gamma-Delta T Cells—An Outdated Clue or a New Direction in Searching for an Anticancer Strategy? A Short Report

“…In our previous report, we demonstrated that patients before and on the 33rd day of therapy showed decreased serum HSP90 levels compared to healthy controls with a higher difference on the day of diagnosis than after 33rd day [11].…”

Age- and Sex- Dependent Changes in Serum Levels of TAS, TOS, TLR2, TLR4, HSP60, HSP90, and HMGB1

“…Their cellular functions show differences; for example, HSP90 may exert anti-apoptotic features although HSP60 may be important in pro-apoptotic process (26). Their circulating levels may be assessed to be a potential marker for some diseases, including diabetes (27) and acute lymphoblastic leukemia (28). Therefore, it is important to identify age-and sex-specific alternation in circulating levels of HSPs for clarifying their role in health and disease.…”

Circulating Biomarkers Associated with the Diagnosis and Prognosis of B-Cell Progenitor Acute Lymphoblastic Leukemia

“…Heat shock protein 90 kDa (HSP90) is a chaperone that promotes the maturation, structural maintenance, and proper regulation of specific target proteins involved, for instance, in cell cycle control and signal transduction [ 104 ] among other processes and has a remarkable participation in hematological malignancies, including leukemia [ 128 ]. Researchers measured HSP90 protein levels in a pediatric group of patients with ALL before treatment and after 33 days of the Berlin–Frankfurt–Munster (BFM) protocol [ 129 , 130 ]. There was a decrease in levels of HSP90 after induction (range at diagnosis 1.22–23.85 ng/mL: range at day 33rd 1.07–52.51 ng/mL); these findings suggest that cancer cells are sensitive to steroids and that HSP90 is related to a poor response to steroids in children with ALL [ 130 ].…”

“…Researchers measured HSP90 protein levels in a pediatric group of patients with ALL before treatment and after 33 days of the Berlin–Frankfurt–Munster (BFM) protocol [ 129 , 130 ]. There was a decrease in levels of HSP90 after induction (range at diagnosis 1.22–23.85 ng/mL: range at day 33rd 1.07–52.51 ng/mL); these findings suggest that cancer cells are sensitive to steroids and that HSP90 is related to a poor response to steroids in children with ALL [ 130 ].…”