Immunoregulation in patients with acute leukemia at diagnosis and minimal residual disease (Doctoral thesis)

Πέτσα, Παναγιώτα

The aim of this study is to propose an immunophenotypic strategy of determining the levels of T regulatory cells in peripheral blood with maximum sensitivity, to study the role of T-regulatory cells in leukemogenesis and the correlation of their levels with the response to chemotherapy and finally, to define the predictive value of the determination of their levels. In this study, Tregs were identified in peripheral blood, using the CD4, CD25, CD127 and FoxP3 markers, of 60 patients with newly diagnosed acute myeloid leukemia, 15 patients with newly diagnosed acute lymphoblastic leukemia and 50 healthy volunteers. More specifically, cells expressing CD4+CD25hiCD127loFoxP3+ were selected. The identification of T-regulatory cells in newly diagnosed acute leukemia, using the above phenotype, showed increased expression of Tregs at diagnosis in comparison to their expression in healthy volunteers. This expression revealed a significant gradient, with the lowest expression being present in healthy controls, followed by the expression at diagnosis of acute myeloid leukemia and finally the expression at diagnosis of acute lymphoblastic leukemia. In addition, the significant increase in the expression of T-regulatory cells at diagnosis of all acute leukemia subtypes is indicative of the role of Tregs in leukemogenesis through suppression of immune responses and thus the protection of stem cells from immune responses. Circulating T regulatory cells were also determined during the monitoring of leukemia for detection of minimal residual disease, disease relapse and monitoring post salvage treatment. However, no correlation of the levels of these cells with the progression of the disease was detected. Despite this, it was observed that T-regulatory cells at diagnosis of leukemia in patients who achieved complete remission after the induction therapy were at a lower ebb in comparison to the regulatory cells of those who had primary refractory disease. This observation is indicative that T-regulatory cells, which play an important role in leukemogenesis, could act as a predictive marker for response to induction therapy but cannot be used as a prognostic marker for the course of the disease, the response to chemotherapy and the early detection of relapse.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Subject classification: Λευχαιμία
Keywords: Ανοσορρύθμιση,Οξεία λευχαιμία,Υπολειμματική νόσο,Τ Ρυθμιστικά λεμφοκύτταρα,Immunoregulation,Acute leukemia,Minimal residual disease,T regulatory cells
Appears in Collections:Διδακτορικές Διατριβές

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