ELVIRA DEOLINDA RODRIGUES PEREIRA VELLOSO
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
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
101 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 101
- The PIP4K2 inhibitor THZ-P1-2 exhibits antileukemia activity by disruption of mitochondrial homeostasis and autophagy(2022) LIMA, Keli; PEREIRA-MARTINS, Diego Antonio; MIRANDA, Livia Bassani Lins de; COELHO-SILVA, Juan Luiz; LEANDRO, Giovana da Silva; WEINHAUSER, Isabel; CAVAGLIERI, Rita de Cassia; LEAL, Aline de Medeiros; SILVA, Wellington Fernandes da; LANGE, Ana Paula Alencar de Lima; VELLOSO, Elvira Deolinda Rodrigues Pereira; GRIESSINGER, Emmanuel; HILBERINK, Jacobien R.; AMMATUNA, Emanuele; HULS, Gerwin; SCHURINGA, Jan Jacob; REGO, Eduardo Magalhaes; MACHADO-NETO, Joao AgostinhoThe treatment of acute leukemia is challenging because of the genetic heterogeneity between and within patients. Leukemic stem cells (LSCs) are relatively drug-resistant and frequently relapse. Their plasticity and capacity to adapt to extracellular stress, in which mitochondrial metabolism and autophagy play important roles, further complicates treatment. Genetic models of phosphatidylinositol-5-phosphate 4-kinase type 2 protein (PIP4K2s) inhibition have demonstrated the relevance of these enzymes in mitochondrial homeostasis and autophagic flux. Here, we uncovered the cellular and molecular effects of THZ-P1-2, a pan-inhibitor of PIP4K2s, in acute leukemia cells. THZ-P1-2 reduced cell viability and induced DNA damage, apoptosis, loss of mitochondrial membrane potential, and the accumulation of acidic vesicular organelles. Protein expression analysis revealed that THZ-P1-2 impaired autophagic flux. In addition, THZ-P1-2 induced cell differentiation and showed synergistic effects with venetoclax. In primary leukemia cells, LC-MS/MS-based proteome analysis revealed that sensitivity to THZ-P1-2 is associated with mitochondrial metabolism, cell cycle, cell-of-origin (hematopoietic stem cell and myeloid progenitor), and the TP53 pathway. The minimal effects of THZ-P1-2 observed in healthy CD34(+) cells suggest a favorable therapeutic window. Our study provides insights into the pharmacological inhibition of PIP4K2s targeting mitochondrial homeostasis and autophagy, shedding light on a new class of drugs for acute leukemia.
- Patterns and Prognostic Impact of CNS Infiltration in Adults with Newly Diagnosed Acute Lymphoblastic Leukemia(2022) PERRUSO, Luiza Lapolla; VELLOSO, Elvira; ROCHA, Vanderson; REGO, Eduardo M.; SILVA, Wellington F.
- Duffy null genotype or Fy(a-b-) phenotype are more accurate than self-declared race for diagnosing benign ethnic neutropenia in Brazilian population(2017) DINARDO, C. L.; KERBAUY, M. N.; SANTOS, T. C.; LIMA, W. M.; DEZAN, M. R.; OLIVEIRA, V. B.; MENDRONE-JUNIOR, A.; ROCHA, V.; VELLOSO, E. D. R. P.
conferenceObject Morphological, Immunohistochemical and Cytogenetic Bone Marrow Characterization of 12 Patients with Acquired Aplastic Anemia (AAA) That Progressed to Myelodysplastic Syndromes (MDS)(2017) MARCHESI, Raquel; VELLOSO, Elvira; GARANITO, Marlene; SIQUEIRA, Sheila; NETO, Raymundo Azevedo; KUMEDA, Cristina; ZERBINI, Maria Claudia- Flow cytometry ""Ogata score"" for the diagnosis of myelodysplastic syndromes in a real-life setting. A Latin American experience(2019) MONTAUBAN, Sofia Grille; HERNANDEZ-PEREZ, Carlos R.; VELLOSO, Elvira D. R. P.; NOVOA, Viviana; LORAND-METZE, Irene; GONZALEZ, Jaqueline; SOLARI, Liliana; CISMONDI, Valeria; SERRANO, Juan Carlos; BURGNINI, Andreina; RABELO-CARRASCO, Laura J.; BACAL, Nydia; TRIAS, Natalia; GUEVARA, Romina; VIDO, Joyce Rico; CRISP, Renee; ENRICO, Alicia; BOADA, Matilde; CUNHA, Fernanda G. Pereira; FANESSI, Viviana; VENEGAS, Maria Belen; ISSOURIBEHERE, Diego; NOVOA, Andrea; LENS, DanielaIntroduction Flow cytometry (FC) is a helpful tool for the diagnosis of myelodysplastic syndrome (MDS). Different FC score systems have been developed. The ""Ogata score"" is a simple diagnostic score that has been validated having a sensitivity of 69% and a specificity of 92% in low-risk MDS. We aimed to study the feasibility and the utility of the ""Ogata score"" for the diagnosis of MDS among Latin America (LA) Laboratories. Methods This is a case and control study conducted in LA institutions members of Grupo Latinoamericano de Mielodisplasia (GLAM). A total of 146 MDS patients and 57 control patients were included. ""Ogata score"" was calculated. Results The sensitivity of ""Ogata score"" was 75.6% (95% CI, 66.8-81.3), specificity was 91.2% (95% CI, 79.7-96.7), PPV was 95.6% (95% CI, 88.5-98.3), and NPV was 65.4% (95% CI, 49.1-71.9). In low/intermediate-1 IPSS patients group, the sensitivity was 70.1% (95% CI, 60.2-78.2), specificity was 91.2% (CI-95%, 79.7-96.7), PPV was 94.2% (95% CI, 86.4-97.8), and NPV was 62.1% (95% CI, 53.0-78.7). In the group of patients ""without MDS specific markers"" (patients without ring sideroblasts, blast excess, or chromosomal abnormalities), the sensitivity was 66.7% (CI-95%, 55.8-76.0), specificity was 91.2% (95% CI, 79.7-96.7), PPV was 92.3% (95% CI, 82.2-97.1), and NPV was 63.5% (95% CI, 51.9-73.5). Conclusions The diagnostic power found in this study was similar to the reported by Della-Porta et al. Also in LA, the analysis was made in modern equipment with acquisition of at least 100 000 events which permits a good reproducibility of the results.
- Venetoclax and Azacytidine Therapy in High-Risk Myelodysplastic Syndromes: A Retrospective Evaluation of a RealWorld Experience. Latin-American MDS Group - Glam(2022) IASTREBNER, Marcelo; CRISP, Renee Leonor; OVILLA, Roberto; LEON, Andres Gomez-De; PUENTE, Adriana Karola; DUARTE, Fernando Barroso; VELLOSO, Elvira D. R. P.; GUSMAO, Breno; VARELA, Ana; BOADA, Matilde; GRILLE, Sofia
- Part 5: Myelodysplastic syndromes—Treatment of high-risk disease(2018) MAGALHÃES, Silvia Maria Meira; CHAUFFAILLE, Maria de Lourdes Lopes Ferrari; VELLOSO, Elvira Deolinda Rodrigues Pereira; BUZZINI, Renata; BERNARDO, Wanderley Marques
- Myelodysplastic Syndromes in Latin-America - Results from a Novel International Registry: Re-Glam(2022) GRILLE, Sofia; VELLOSO, Elvira D. R. P.; BOADA, Matilde; CHAVEZ, Elia Apodaca; LEON, Andres Gomez-De; RODRIGUEZ-ZUNIGA, Anna Cecilia; MORENO, Emmanuel Martinez; PEREZ-JACOBO, Fernando; ALFONSO, Graciela; SERRANO, Juan Carlos; TEJEIRA, Natalia; DIAZ, Lilian; OLIVARES, Valentina; KORNBLIHTT, Laura; SCHUSTERSCHITZ, Sergio; IASTREBNER, Marcelo
- Toxicity Profile of PEG-Asparaginase in Adult Patients With Acute Lymphoblastic Leukemia in Brazil: A Multicenter Cross-Sectional Study(2020) SILVA, Wellington F. da; MASSAUT, Ires H. B.; BENDLIN, Rodrigo M.; ROSA, Lidiane I.; VELLOSO, Elvira D. R. P.; REGO, Eduardo M.; ROCHA, VandersonPegylated asparaginase was recently approved for use in Brazil. We reviewed its toxicity in adults with acute lymphoblastic leukemia. Fifty-seven patients were included, with remarkable thromboembolic (17%) and hepatic (77%) event rates. No fatal event was registered. Our incidence is similar to those reported in other trials. These effects should not preclude further use because most events are manageable. Background: Currently, pediatric-inspired regimens are commonly applied to adults with acute lymphoblastic leukemia (ALL) after the recent recognition that these protocols improve survival. While asparaginase in whatever available formulation is a key component of modern treatment of ALL, many adult oncologists and hematologists struggle to deal with its particular toxicities in clinical practice. We reviewed toxicity outcomes of pegylated asparaginase (PEG-ASP) in adults with ALL treated in 3 reference centers in Brazil. Patients and Methods: This was a cross-sectional retrospective chart-review study encompassing patients aged 15 years and older diagnosed with ALL or ambiguous-lineage leukemia who received at least one dose of PEG-ASP, regardless of the adopted regimen. Results: A total of 57 patients were included (age range, 15-57 years). Most patients (70%) received 2000 IU/m(2) as the initial dose, by intravenous route (72%). The incidence of thromboembolic events was 17.5%, and the main site was cerebral venous sinus (4/10). Thrombosis was more frequent in patients receiving second-line treatment. In obese patients, grade 3 hepatotoxicity and hyperbilirubinemia were more common. Clinical pancreatitis (grade 3 or higher) was found in 2 of 57 cases. PEG-ASP had to be discontinued in 19.3% of exposed patients (11/57). Conclusion: By reviewing the medical charts of adult patients with ALL from 3 reference centers, we found that our incidence of thrombotic and hepatic adverse events is similar to those reported in other trials involving PEG-ASP. Usually these effects should not preclude further use of the drug because most events are manageable in routine clinical practice.
- Splenic Diffuse Red Pulp Small B Cell Lymphoma: Transformation To Diffuse Large Cells B Lymphoma(2013) BEZERRA, Evandro Dantas; FONTENELE, Leila Patricia; PEREIRA, Juliana; LAGE, Luis Alberto de Padua Covas; MACIEL, Felipe; BARQUINERO, Leticia; CARVALHO, Priscila R.; SIQUEIRA, Scheila; VELLOSO, Elvira R. P.