EDUARDO MAGALHAES REGO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
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article Acute promyelocytic leukaemia in lowincome and middle income countries: a Brazilian experience(2024) PEREIRA-MARTINS, Diego A.; WEINHAEUSER, Isabel; COELHO-SILVA, Juan L.; AMMATUNA, Emanuele; HULS, Geruin; SCHURINGA, Jan Jacob; REGO, Eduardo M.; LUCENA-ARAUJO, Antonio R.- Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells(2024) PARDUCCI, Natalia Sudan; GARNIQUE, Anali Del Milagro Bernabe; LIMA, Keli; CARLOS, Jorge Antonio Elias Godoy; FONSECA, Natasha Peixoto; MIRANDA, Livia Bassani Lins de; ALMEIDA, Bruna Oliveira de; REGO, Eduardo Magalhaes; TRAINA, Fabiola; MACHADO-NETO, Joao AgostinhoMyeloproliferative neoplasms (MPN) are consolidated as a relevant group of diseases derived from the mal- function of the hematopoiesis process and have as a particular attribute the increased proliferation of myeloid lineage. Among these, chronic neutrophilic leukemia (CNL) is distinguished, caused by the T6181 mutation of the CSF3R gene, a trait that generates ligand-independent receptor activation and downstream JAK2/STAT signaling. Previous studies reported that mutations in BCR::ABL1 and JAK2V617F increased the expression of the aurora kinase A (AURKA) and B (AURKB) in Ba/F3 cells and their pharmacological inhibition displays anti- neoplastic effects in human BCR::ABL1 and JAK2V617F positive cells. Delimiting the current scenario, aspects related to the AURKA and AURKB as a potential target in CSF3R76181-driven models is little known. In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A in- hibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3RT1at mutation. AZD1152-HQPA and reversine demonstrated antineoplastic potential, causing a decrease in cell viability, clo- nogenicity, and proliferative capacity. At molecular levels, all inhibitors reduced histone H3 phosphorylation, aurora A inhibitor I and reversine reduced STATS phosphorylation, and AZD1152-HQPA and reversine induced PARP1 cleavage and yH2AX expression. Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL
- ARHGAP6 transcript levels are associated with molecular risk and impact survival outcomes in acute myeloid leukemia(2024) SILVA, Jean Carlos Lipreri da; COELHO-SILVA, Juan Luiz; VICARI, Hugo Passos; LIMA, Keli; REGO, Eduardo Magalhaes; TRAINA, Fabiola; MACHADO-NETO, Joao Agostinho
- Patterns and prognostic impact of CNS infiltration in adults with newly diagnosed acute lymphoblastic leukemia(2024) PERRUSO, Luiza Lapolla; VELLOSO, Elvira; ROCHA, Vanderson; REGO, Eduardo Magalhaes; SILVA, Wellington FernandesAcute lymphoblastic leukemia (ALL) is highly associated with central nervous system (CNS) infiltration and can be associated with higher risk of relapse. Conventional cytology (CC) is the traditional method for diagnosing CNS infiltration, although the use of immunophenotyping by flow cytometry (FC) has gained prominence in recent years due to its higher sensitivity. Also, some authors have proposed that CSF contamination by a traumatic lumbar puncture (TLP) could have a clinical impact. This retrospective study accessed the impact of CNS infiltration by CC or FC on overall survival, event-free survival, and relapse rate. In a cohort of 105 newly diagnosed ALL patients, CNS1, CNS2, and CNS3 status were found in 84%, 14%, and 2%, respectively. We found that extramedullary disease at the diagnosis, higher leukocyte counts, and higher blast percentage were associated with a positive CC. Sensitivity and specificity of CC were 53% and 98%, respectively. Three-year overall survival was 42.5%. Conversely, TLP was not associated with a positive CC nor had an impact on relapse rates. In multivariate analysis, a positive CC was associated with an increased relapse rate (HR 2.074, p = 0.037), while its detection by FC did not associate with this endpoint. Survival rates seem to be increasing over the last years by the adoption of a stratified CNS prophylaxis risk strategy. CSF contamination does not represent a major concern according to our report, as it did not increase CNS involvement or relapse rates.
- Therapeutic plasma exchange and HLA desensitization(2024) REGO, Eduardo Magalhaes