Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Zampogiannis Archontis
Dissertation committee:
Μοσχόβη Μαρία, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Παπαβασιλείου Αθανάσιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γουργιώτης Δημήτριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πιπέρη Χριστίνα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Αγγελοπούλου Μαρία, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Βασιλακόπουλος Θεόδωρος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κασσή Ευανθία, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Διερεύνηση των κυτοκινών και των αγγειογενετικών παραγόντων στις λευχαιμίες της παιδικής ηλικίας
Translated title:
Investigation of cytokines and angiogenic factors in childhood leukemia
Summary:
IL-23 is an IL-12 cytokine family member with pleiotropic functions that regulates tumor growth in various cancer types, exhibiting both anti-tumorigenic and pro-tumorigenic properties. Preclinical studies have shown a potential anti-leukemic action on childhood B-ALL cells. Placental Growth Factor (PlGF) is an angiogenic factor that is a member of the VEGF family. Although PlGF appears to be redundant for normal vascular development, it has a significant role in various pathologic conditions, including hematologic malignancies. The binding of PlGF to the soluble form of the VEGFR-1 receptor (sFlt-1) serves as an anti-angiogenic regulatory mechanism, since it does not allow the intracellular signal transmission. The study involved 65 children with acute leukemia [59 patients with acute lymphoblastic leukemia (ALL) and 6 patients with acute myeloid leukemia (AML)] and 27 healthy controls. Using an enzyme-linked immunosorbent assay, we aimed to determine the IL-23, PlGF and sFlt-1 levels in the peripheral blood (PB) and bone marrow (BM) of patients at diagnosis and at the end of the induction therapy (EIT). PB IL-23 levels were lower in leukemia patients compared to the healthy controls. In all acute leukemia patients, IL-23 levels were significantly lower at diagnosis both in PB (p=0.015) and in BM (p=0.037) compared to the PB and BM concentrations at the EIT. The same pattern was present in both subgroups of ALL and AML patients. PB PlGF levels were significantly higher in both ALL (p=0.006) and AML (p=0.004) patients compared to healthy controls. In ALL patients, PB PlGF levels at diagnosis were significantly higher in patients with positive MRD at the EIT compared to patients with negative MRD (p=0.008). In AML patients, PB PlGF levels at diagnosis were significantly higher in patients with WBC count over 20.000/μl compared to those with WBC count below 20.000/μl (p=0.049). PB sFlt-1 levels were also higher in both ALL (p<0.001) and AML (p=0.065) patients compared to healthy controls. The high leukemic burden at diagnosis was related with lower IL-23 levels, which were increased with the disease remission. Considering the anti-leukemic potential of this cytokine, the elevation of the IL-23 concentration at the disease remission, indicates a beneficial role of IL-23 in pediatric acute leukemia. The increased PlGF levels in leukemia patients are indicative of the involvement of PlGF in leukemia’s pathophysiology. Moreover, the correlation between PlGF levels and independent prognostic factors for leukemia, such as the MRD and WBC count, is indicative of the PlGF prognostic value.
Main subject category:
Health Sciences
Keywords:
Leukemia, Cytokines, Angiogenic factors
Number of references:
319
