Chemotherapy induces plasmatic antioxidant changes in pediatric patients with acute lymphoid leukemia B that correlate to disease prognosis.

Pediatric acute lymphoid leukemias (ALL) is the most common childhood cancer, and cytotoxic chemotherapy remains the primary treatment option. Chemotherapic drugs act by oxidative stress generation, but their clinical meaning is poorly understood. During the chemotherapy schedule, this study evaluated the antioxidant profile of peripheral blood samples from 34 patients diagnosed with type B-cell ALL (B-ALL). Peripheral blood samples were collected at diagnosis (D0) and during the induction, consolidation, and maintenance phases. The plasma total antioxidant capacity (TRAP) was determined using the high-sensitivity chemiluminescence technique. Antioxidant levels were higher on D0 compared to day 7 after treatment starting (D7) in the induction phase (28.68-1194.71 µM Trolox, p = 0.0178) and in the high-risk group (age > ten years and/or with white blood cell counts and/or > 50,000 white blood cells/m3 at diagnosis) concerning low-risk patients (253.79-1194.71 µM Trolox, p = 0.0314). Reduced TRAP was also detected in patients who died compared to those who survived (392.42-1194.71 µM Trolox, p = 0.0278). Patients under consolidation (56.14-352.05 µM Trolox, p=<0.0001) and maintenance (30.48-672.99 µM Trolox, p=<0.0001) showed a significant reduction in TRAP levels compared to those from the induction phase (28.68-1390.26 µM Trolox), reaching levels similar to cured patients out of treatment (64.82-437.82 µM Trolox). These findings suggest that the variation of the total antioxidant capacity in B-ALL during chemotherapy is a parameter that correlates to some predictors of disease prognosis.

Comparative Analysis of Systemic and Tumor Microenvironment Proteomes From Children With B-Cell Acute Lymphocytic Leukemia at Diagnosis and After Induction Treatment.

Among the childhood diseases, B-cell acute lymphocytic leukemia (B-ALL) is the most frequent type of cancer. Despite recent advances concerning disease treatment, cytotoxic chemotherapy remains the first line of treatment in several countries, and the modifications induced by such drugs in the organism are still poorly understood. In this context, the present study provided a comparative high-throughput proteomic analysis of the cumulative changes induced by chemotherapeutic drugs used in the induction phase of B-ALL treatment in both peripheral blood (PB) and bone marrow compartment (BM) samples. To reach this goal, PB and BM plasma samples were comparatively analyzed by using label-free proteomics at two endpoints: at diagnosis (D0) and the end of the cumulative induction phase treatment (D28). Proteomic data was available via ProteomeXchange with identifier PXD021584. The resulting differentially expressed proteins were explored by bioinformatics approaches aiming to identify the main gene ontology processes, pathways, and transcription factors altered by chemotherapy, as well as to understand B-ALL biology in each compartment at D0. At D0, PB was characterized as a pro-inflammatory environment, with the involvement of several downregulated coagulation proteins as KNG, plasmin, and plasminogen. D28 was characterized predominantly by immune response-related processes and the super expression of the transcription factor IRF3 and transthyretin. RUNX1 was pointed out as a common transcription factor found in both D0 and D28. We chose to validate the proteins transthyretin and interferon-gamma (IFN-γ) by commercial kits and expressed the results as PB/BM ratios. Transthyretin ratio was augmented after induction chemotherapy, while IFN-γ was reduced at the end of the treatment. Considering that most of these proteins were not yet described in B-ALL literature, these findings added to understanding disease biology at diagnosis and highlighted a possible role for transthyretin and IFN-γ as mechanisms related to disease resolution.

Oral Manifestation as the Main Sign of an Advanced Stage Acute Promyelocytic Leukemia.

Acute myeloid leukemia is an aggressive malignant neoplasm occurring mainly in elderly, with the median age of 65 years. Oral manifestations, mainly spontaneous bleeding, are a common finding in acute myelocytic leukemia and may represent the initial evidence of the disease. This report describes a case of a 47-year-old man with a one-month history of spontaneous oral bleeding. The patient had already been consulted by two professionals but he remained undiagnosed. The physical examination revealed paleness, fever, epistaxis and ecchymoses in the oral mucosa. The complete blood count revealed anemia, severe thrombocytopenia and leukocytosis with blasts predominance, reinforcing the diagnosis hypothesis of an acute leukemia. The patient was immediately referred to the Hospital and despite having received a quick intervention, he died 3 days after the admission due to diffuse pulmonary alveolar hemorrhage. According to the peripheral blood immunophenotyping the diagnosis of hypogranular variant of acute promyelocytic leukemia was established. The delay in the diagnosis may have influenced the unfavorable outcome. Early diagnosis and management are indispensable for survival of leukemia patients. In this way, dentists may be responsible for an early detection of oral manifestations of leukemia and for a fast referral to an adequate professional.

IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients: IL-10 polymorphism and plasma levels in leukemia patients.

Acute Lymphoblastic Leukemia is the leading form of cancer in infancy, and compelling evidences suggest an involvement of altered immune competence on this malignancy pathogenesis. Interleukin 10 (IL-10) is a pleiotropic cytokine designated as an immunosuppressive molecule, but may act as an immunostimulant factor in cancer development and progression. An IL-10 single nucleotide polymorphism (SNP) rs1800896 has been associated with disease progression to ALL, and might influence cytokine expression. This study analyzed the IL-10 rs1800896 polymorphism and performed a case-control study to determine the significant associations with ALL susceptibility and prognosis. IL-10 plasma levels were determined and associated with genotypes and disease phase. The study consisted of 67 childhood ALL patients and 75 age-related healthy controls. The rs1800896 was not associated with ALL susceptibility or risk of relapse. No significant association was observed between different genotypes of the rs1800896 and plasma levels of IL-10. Cytokine plasma levels were significantly higher in the diagnosis group (9.71 pg/mL ± 3.7), comparing to the treatment (3.48 pg/mL ± 1.3; p=0.01) and remission phase (0.12 pg/mL ± 0.1; p=0.0001) groups. This work indicates that the IL-10 plasma expression is altered from ALL disease diagnosis and remission. Moreover, prospective studies will establish the functional role of IL-10 in immune modulation in childhood ALL.