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
57 resultados
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Agora exibindo 1 - 10 de 57
- 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.
- 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.
- 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.
- 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
- 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.
- Paper Assessing the impact of prophylactic anidulafungin during remission induction of acute myeloid leukemia - A propensity-score matching analysis(2023) SILVA, Wellington Fernandes da; MENDES, Fernanda Rodrigues; MELO, Raphael da Costa Bandeira de; VELLOSO, Elvira Deolinda Rodrigues Pereira; ROCHA, Vanderson; REGO, Eduardo MagalhaesIntroduction: Invasive fungal infection (IFI) accounts for substantial morbidity during the treatment of acute myeloid leukemia (AML) in adults. Antifungal prophylaxis (AP) is needed during intensive chemotherapy, and posaconazole is not widely available. In this study, we aimed to examine the impact of prophylactic anidulafungin during intensive AML remission induction. Methods: This is a retrospective cohort encompassing newly diagnosed AML adult patients. All subjects received intensive chemotherapy and were divided into three groups: patients who did not receive any AP and patients who received fluconazole (150-400 mg/day) or anidulafungin (100 mg/day). Results: During AML induction, 82 patients did not receive AP, 108 and 14 patients received anidulafungin and fluconazole, respectively. IFI incidence was 27%, classified as possible, probable, and proven in 65, 2 and 33%, respectively. Multivariable analysis showed that lower neutrophil counts are associated with IFI (OR = 2.8), whereas age, genetic classification, and lymphocyte counts were not. To examine the impact of anidulafungin in comparison with 'no AP', a propensity score matching analysis was performed. Use of anidulafungin was not related to less IFI during induction, while neutrophil counts remained significant. Patients under prophylactic anidulafungin received less amphotericin B (p < 0.001) but not voriconazole (p = 0.49). Discussion: To our knowledge, this is the first study addressing the role of anidulafungin during AML induction. Here, the incidence of mold infections did not decrease with AP, suggesting that in a setting with a high incidence of IFI, broad spectrum AP might be more suitable.
- Acute megakaryoblastic leukemia with t(1;22)(p13.3;q13.1); RBM15-MKL1 mimicking hepatoblastoma in an infant: The role of karyotype in differential diagnosis(2020) MARQUES-PIUBELLI, Mario L.; CORDEIRO, Maria Gabriella; CRISTOFANI, Lilian; BARROSO, Rodrigo de Souza; PAES, Vitor Ribeiro; CASTELLI, Jussara Bianchi; VELLOSO, Elvira Deolinda Rodrigues Pereira
- Secondary myeloid neoplasms: bone marrow cytogenetic and histological features may be relevant to prognosis(2017) TANIZAWA, Roberta Sandra da Silva; ZERBINI, Maria Claudia Nogueira; ROSENFELD, Ricardo; KUMEDA, Cristina Aiko; AZEVEDO, Raymundo Soares; SIQUEIRA, Sheila Aparecida Coelho; VELLOSO, Elvira Deolinda Rodrigues PereiraAbstract Background: Secondary myeloid neoplasms comprise a group of diseases arising after chemotherapy, radiation, immunosuppressive therapy or from aplastic anemia. Few studies have addressed prognostic factors in these neoplasms. Method: Forty-two patients diagnosed from 1987 to 2008 with secondary myeloid neoplasms were retrospectively evaluated concerning clinical, biochemical, peripheral blood, bone marrow aspirate, biopsy, and immunohistochemistry and cytogenetic features at diagnosis as prognostic factors. The International Prognostic Scoring System was applied. Statistical analysis employed the Kaplan–Meier method, log-rank and Fisher's exact test. Results: Twenty-three patients (54.8%) were male and the median age was 53.5 years (range: 4–88 years) at diagnosis of secondary myeloid neoplasms. Previous diseases included hematologic malignancies, solid tumors, aplastic anemia, autoimmune diseases and conditions requiring solid organ transplantations. One third of patients (33%) were submitted to chemotherapy alone, 2% to radiotherapy, 26% to both modalities and 28% to immunosuppressive agents. Five patients (11.9%) had undergone autologous hematopoietic stem cell transplantation. The median latency between the primary disease and secondary myeloid neoplasms was 85 months (range: 23–221 months). Eight patients were submitted to allogeneic hematopoietic stem cell transplantation to treat secondary myeloid neoplasms. Important changes in bone marrow were detected mainly by biopsy, immunohistochemistry and cytogenetics. The presence of clusters of CD117+ cells and p53+ cells were associated with low survival. p53 was associated to a higher risk according to the International Prognostic Scoring System. High prevalence of clonal abnormalities (84.3%) and thrombocytopenia (78.6%) were independent factors for poor survival. Conclusion: This study demonstrated that cytogenetics, bone marrow biopsy and immunohistochemistry are very important prognostic tools in secondary myeloid neoplasms.
- Assessment of Bone Microarchitecture in Patients with Systemic Mastocytosis and its Association with Clinical and Biochemical Parameters of the Disease(2023) FRANCO, Andre S.; MURAI, Igor H.; TAKAYAMA, Liliam; CAPARBO, Valeria F.; MARCHI, Luan L.; VELLOSO, Elvira D. R. P.; PEREIRA, Rosa M. R.Patients with systemic mastocytosis (SM) are at high risk of bone deterioration. However, the evaluation of bone microarchitecture in this disease remains unclear. We aimed to assess bone microarchitecture in patients with SM. This was a cross-sectional study of 21 adult patients with SM conducted in a quaternary referral hospital in Sao Paulo, Brazil. A healthy, age-, weight-, and sex-matched cohort of 63 participants was used to provide reference values for bone microarchitecture, assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). Total volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness at the radius were significantly lower in the control group compared with the SM group (all P < 0.001). Patients with aggressive SM had significantly lower trabecular number (Tb.N) (P = 0.035) and estimated failure load (F.load) (P = 0.032) at the tibia compared with those with indolent SM. Handgrip strength was significantly higher in patients who had more Tb.N at the radius (rho, 0.46; P = 0.036) and tibia (rho, 0.49; P = 0.002), and lower who had more trabecular separation at the radius (rho, -0.46; P = 0.035) and tibia (rho, -0.52; P = 0.016). Strong and positive associations between F.load (rho, 0.75; P < 0.001) and stiffness (rho, 0.70; P < 0.001) at the radius, and between F.load at the tibia (rho, 0.45; P = 0.038) were observed with handgrip strength. In this cross-sectional study, aggressive SM was more susceptible to bone deterioration compared with indolent SM. In addition, the findings demonstrated that handgrip strength was associated with bone microarchitecture and bone strength.
- Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel(2022) VELLOSO, Elvira D. Rodrigues Pereira; PADULLA, Georgia A.; CERQUEIRA, Ana Maria Mosca de; SOUSA, Adriana Martins de; SANDES, Alex Freire; TRAINA, Fabiola; SEGURO, Fernanda Salles; NOGUEIRA, Frederico Lisboa; PEREIRA, Grazielly de Fathima; BOECHAT, jose Laerte; PAGNANO, Katia Borgia Barbosa; MARCHI, Luan Lima; ENSINA, Luis Felipe; GIAVINA-BIANCHI, Mara; AUN, Marcelo Vivolo; AGONDI, Rosana Camara; SANTOS, Fabio Pires de Souza; GIAVINA-BIANCHI, PedroIntroduction: Systemic Mastocytosis comprises a group of neoplastic diseases character-ized by clonal expansion and infiltration of mast cells into several organs. The diagnosis and treatment of this disease may be challenging for non-specialists. Objective: Make suggestions or recommendations in Systemic Mastocytosis based in a panel of Brazil-ian specialists.Method and results: An online expert panel with 18 multidisciplinary specialists was con-vened to propose recommendations on the diagnosis and treatment of Systemic Mastocy-tosis in Brazil. Recommendations were based on discussions of topics and multiple-choice questions and were graded using the Oxford Centre for Evidence-Based Medicine 2011 Lev-els of Evidence Chart. Conclusion: Twenty-two recommendations or suggestions were proposed based on a litera-ture review and graded according to the findings.(c) 2022 Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular.