Perfil peptidômico no plasma de pacientes com leucemias agudas: identificação de assinaturas de potenciais biomarcadores com espectrometria de massa.

Abstract

ABSTRACT Acute leukemias (ALs) are malignant hematological neoplasms characterized by the uncontrolled proliferation of immature cells in the bone marrow, impairing normal hematopoiesis. ALs are classified as acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), and differ in terms of age distribution and response to therapy. Despite advances in diagnostic tools, conventional approaches still present limitations, including the need for invasive procedures and the challenge of distinguishing between AL subtypes. In this context, clinical peptidomics (CP) has emerged as a promising tool for identifying molecular biomarkers that may improve diagnosis, prognosis, and personalized treatment strategies. This study aimed to conduct a literature review on the application of CP in ALs, as well as to identify molecular signatures for clinical differentiation, assess prognostic biomarkers, and explore treatment-related changes by analyzing samples collected at two time points: at diagnosis (T1) and after three weeks of treatment (T4). Specifically, the study aimed to characterize the plasma peptidomic profiles of patients with ALL and AML compared to a control group; evaluate dynamic changes in peptide expression throughout therapy; identify signatures with clinical relevance using MALDI-TOF/MS (Matrix-Assisted Laser Desorption/Ionization Time-of Flight Mass Spectrometry); investigate associations between peptidomic patterns and clinical variables such as age, outcome, and treatment response; and explore specific profiles in molecular subgroups including Philadelphia-positive and Philadelphia-negative ALL, AML with or without FLT3 mutation, and acute promyelocytic leukemia (APL). This thesis is divided into two main chapters. The first chapter presents a literature review on the use of CP in ALs, highlighting its potential biomarkers and technical limitations. The second chapter describes a MALDI-TOF/MS-based analysis of plasma samples from patients with ALL and AML. The results revealed potential biomarkers associated with differential diagnosis and clinical outcomes and supported the applicability of plasma as a viable matrix for peptidomic studies in acute leukemias.