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
29 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 29
- 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.
- 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
- 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.
- 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.
- Cytogenetic studies for cMYC, BCL2 and BCL6 genes in neoplasm: comparison of karyotype, FISH in paraffin-embedded tissue and FISH in methanol-acetic acid-fixed cells suspensions(2021) GARCIA, Caroline Henriques; SILVA, Roberta Maria da; SAFRANAUSKAS, Oliveira; BEZERRA, Alanna Mara P. S.; VELLOSO, Elvira D. R. P.
- Part 3: Myelodysplastic syndromes—Treatment of low-risk patients without the 5q deletion(2018) VELLOSO, Elvira Deolinda Rodrigues Pereira; MAGALHÃES, Silvia Maria Meira; CHAUFFAILLE, Maria de Lourdes Lopes Ferrari; BUZZINI, Renata; BERNARDO, Wanderley Marques
- A Novel Assay for the Identification of NOTCH1 PEST Domain Mutations in Chronic Lymphocytic Leukemia(2016) CAMPREGHER, Paulo Vidal; PETRONI, Roberta Cardoso; MUTO, Nair Hideko; SITNIK, Roberta; CARVALHO, Flavia Pereira de; BACAL, Nydia Strachman; VELLOSO, Elvira Deolinda Rodrigues Pereira; OLIVEIRA, Gislaine Borba; PINHO, Joao Renato Rebello; TORRES, Davi Coe; MANSUR, Marcela Braga; HASSAN, Rocio; LORAND-METZE, Irene Gyongyver Heidemarie; CHIATTONE, Carlos Sergio; HAMERSCHLAK, Nelson; MANGUEIRA, Cristovao Luis PitangueiraAims. To develop a fast and robust DNA-based assay to detect insertions and deletions mutations in exon 34 that encodes the PEST domain of NOTCH1 in order to evaluate patients with chronic lymphocytic leukemia (CLL). Methods. We designed a multiplexed allele-specific polymerase chain reaction (PCR) combined with a fragment analysis assay to detect specifically the mutation c. 7544_7545delCT and possibly other insertions and deletions in exon 34 of NOTCH1. Results. We evaluated our assay in peripheral blood samples fromtwo cohorts of patients with CLL. The frequency of NOTCH1 mutations was 8.4% in the first cohort of 71 unselected CLL patients. We then evaluated a second cohort of 26 CLL patients with known cytogenetic abnormalities that were enriched for patients with trisomy 12. NOTCH1 mutations were detected in 43.7% of the patients with trisomy 12. Conclusions. We have developed a fast and robust assay combining allele-specific PCR and fragment analysis able to detect NOTCH1 PEST domain insertions and deletions.
- Validation of interphase fluorescence in situ hybridization (iFISH) for multiple myeloma using CD138 positive cells(2016) KISHIMOTO, Renata Kiyomi; FREITAS, Sarah Lee Vaughan Vulcani de; RATIS, Cristina Alonso; BORRI, Daniela; SITNIK, Roberta; VELLOSO, Elvira Deolinda Rodrigues PereiraABSTRACT BACKGROUND: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance. Multiple myeloma differs from other hematologic malignancies due to a high fraction of low proliferating malignant plasma cells and the paucity of plasma cells in bone marrow aspiration samples, making cytogenetic analysis a challenge. An abnormal karyotype is found in only one-third of patients with multiple myeloma and interphase fluorescence in situ hybridization is the most useful test for studying the chromosomal abnormalities present in almost 90% of cases. However, it is necessary to study the genetic abnormalities in plasma cells after their identification or selection by morphology, immunophenotyping or sorting. Other challenges are the selection of the most informative FISH panel and determining cut-off levels for FISH probes. This study reports the validation of interphase fluorescence in situ hybridization using CD138 positive cells, according to proposed guidelines published by the European Myeloma Network (EMN) in 2012. METHOD: Bone marrow samples from patients with multiple myeloma were used to standardize a panel of five probes [1q amplification, 13q14 deletion, 17p deletion, t(4;14), and t(14;16)] in CD138+ cells purified by magnetic cell sorting. RESULTS: This test was validated with a low turnaround time and good reproducibility. Five of six samples showed genetic abnormalities. Monosomy/deletion 13 plus t(4;14) were found in two cases. CONCLUSION: This technique together with magnetic cell sorting is effective and can be used in the routine laboratory practice. In addition, magnetic cell sorting provides a pure plasma cell population that allows other molecular and genomic studies.
- Scientific comment on tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome(2014) VELLOSO, Elvira Deolinda Rodrigues Pereira
- A novel mechanism of NPM1 cytoplasmic localization in acute myeloid leukemia: the recurrent gene fusion NPM1-HAUS1(2016) CAMPREGHER, Paulo Vidal; PEREIRA, Welbert de Oliveira; LISBOA, Bianca; PUGA, Renato; RODRIGUES, Elvira Deolinda; HELMAN, Ricardo; MARTI, Luciana Cavalheiro; GUERRA, Joao Carlos Campos; MANOLA, Kalliopi N.; PETRONI, Roberta Cardoso; BEZERRA, Alanna Mara Pinheiro Sobreira; COSTA, Fernando Ferreira; HAMERSCHLAK, Nelson; SANTOS, Fabio Pires de Souza
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