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ARHGAP6 transcript levels are associated with molecular risk and impact survival outcomes in acute myeloid leukemia
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Silva, Jean Carlos Lipreri da

; Coelho-Silva, Juan Luiz

; Vicari, Hugo Passos

; Lima, Keli Rego, Eduardo Magalhães Traina, Fabiola Machado-Neto, João Agostinho

Hematology, Transfusion and Cell Therapy

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mar 2024, Volume 46 N. 1 Pages 101 - 105

Abstract: En | Text: En | PDF: En

https://doi.org/10.1016/j.htct.2023.06.004

Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel
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Velloso, Elvira D. Rodrigues Pereira

; Padulla, Geórgia A.

; Cerqueira, Ana Maria Mósca de

; Sousa, Adriana Martins de

; Sandes, Alex Freire

; Traina, Fabiola

; Seguro, Fernanda Salles

; Nogueira, Frederico Lisboa

; Pereira, Grazielly de Fátima

; Boechat, José Laerte

; Pagnano, Katia Borgia Barbosa

; Marchi, Luan Lima

; Ensina, Luis Felipe

; Giavina-Bianchi, Mara

; Aun, Marcelo Vivolo Agondi, Rosana Câmara Santos, Fabio Pires de Souza Giavina-Bianchi, Pedro

Hematology, Transfusion and Cell Therapy

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oct 2022, Volume 44 N. 4 Pages 582 - 594

Abstract: En | Text: En | PDF: En

ABSTRACT Introduction: Systemic Mastocytosis comprises a group of neoplastic diseases characterized 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 Brazilian specialists. Method and results: An online expert panel with 18 multidisciplinary specialists was convened to propose recommendations on the diagnosis and treatment of Systemic Mastocytosis 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 Levels of Evidence Chart. Conclusion: Twenty-two recommendations or suggestions were proposed based on a literature review and graded according to the findings.

https://doi.org/10.1016/j.htct.2022.04.006

IRAK1 expression in bone marrow cells does not impact patient outcomes in myelodysplastic syndromes
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Campos, Paula de Melo Machado-Neto, João Agostinho Lorand-Metze, Irene Costa, Fernando Ferreira Saad, Sara Teresinha Olalla Traina, Fabiola

Hematology, Transfusion and Cell Therapy

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mar 2018, Volume 40 N. 1 Pages 92 - 95

Abstract: En | Text: En | PDF: En

https://doi.org/10.1016/j.bjhh.2017.10.001 347 downloads

Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
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Machado-Neto, João Agostinho Fenerich, Bruna Alves Rodrigues Alves, Ana Paula Nunes Fernandes, Jaqueline Cristina Scopim-Ribeiro, Renata Coelho-Silva, Juan Luiz Traina, Fabiola

Clinics

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2018, Volume 73 elocation e566s

Abstract: En | Text: En | PDF: En

The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.

https://doi.org/10.6061/clinics/2018/e566s 3018 downloads

Acute myeloid leukemia with e1a2 BCR-ABL1 fusion gene: two cases with peculiar molecular and clinical presentations
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Silva, Fernanda Borges da Machado-Neto, João Agostinho Koury, Luisa Corrêa de Araujo Bertini, Virginia Helena Leira Lipoli Ratis, Cristina Alonso Chauffaille, Maria de Lourdes Lopes Ferrari Velloso, Elvira Deolinda Rodrigues Pereira Simões, Belinda Pinto Rego, Eduardo Magalhães Traina, Fabiola

Revista Brasileira de Hematologia e Hemoterapia

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dec 2017, Volume 39 N. 4 Pages 379 - 384

Abstract: En | Text: En | PDF: En

https://doi.org/10.1016/j.bjhh.2017.07.001 1060 downloads

Stathmin 1 expression in plasma cell neoplasms
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Machado-Neto, João Agostinho Pericole, Fernando Vieira Costa, Fernando Ferreira Traina, Fabiola Olalla Saad, Sara Teresinha

Revista Brasileira de Hematologia e Hemoterapia

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jun 2017, Volume 39 N. 2 Pages 183 - 185

Abstract: En | Text: En | PDF: En

https://doi.org/10.1016/j.bjhh.2017.02.005 355 downloads

Differential profile of CDKN1A and TP53 expressions in bone marrow mesenchymal stromal cells from myeloid neoplasms
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Lopes, Matheus Rodrigues Machado-Neto, João Agostinho Traina, Fabiola Campos, Paula de Melo Saad, Sara Teresinha Olalla Favaro, Patricia

Revista Brasileira de Hematologia e Hemoterapia

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dec 2016, Volume 38 N. 4 Pages 368 - 370

Abstract: En | Text: En | PDF: En

https://doi.org/10.1016/j.bjhh.2016.07.002 598 downloads

Reactive oxygen species overload promotes apoptosis in JAK2V617F-positive cell lines
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Machado-Neto, João Agostinho Traina, Fabiola

Revista Brasileira de Hematologia e Hemoterapia

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sep 2016, Volume 38 N. 3 Pages 179 - 181

Abstract: En | Text: En | PDF: En

https://doi.org/10.1016/j.bjhh.2016.04.009 491 downloads

Somatic mutations of calreticulin in a Brazilian cohort of patients with myeloproliferative neoplasms
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Machado-Neto, João Agostinho Campos, Paula de Melo Albuquerque, Dulcinéia Martins de Costa, Fernando Ferreira Lorand-Metze, Irene Saad, Sara Terezinha Olalla Traina, Fabiola

Revista Brasileira de Hematologia e Hemoterapia

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jun 2015, Volume 37 N. 3 Pages 211 - 214

Abstract: En | Text: En | PDF: En

https://doi.org/10.1016/j.bjhh.2015.03.012 1142 downloads

10.

Metaphase cytogenetics and single nucleotide polymorphism arrays in myeloid malignancies
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Silva, Fernanda Borges da Traina, Fabiola

Revista Brasileira de Hematologia e Hemoterapia

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apr 2015, Volume 37 N. 2 Pages 71 - 72

Abstract: En | Text: En | PDF: En

https://doi.org/10.1016/j.bjhh.2015.01.007 850 downloads

11.

Myelodysplastic syndrome with synchronous gastric cancer: when the symptoms suggest something else
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Campos, Paula de Melo Traina, Fabiola Lorand-Metze, Irene Saad, Sara Teresinha Olalla

Revista Brasileira de Hematologia e Hemoterapia

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dec 2014, Volume 36 N. 6 Pages 442 - 444

Abstract: En | Text: En | PDF: En

Although myelodysplastic syndromes have a clear definition in theory, the morphologic dysplasia associated with ineffective hematopoiesis may be subtle and difficult to recognize and can commonly be mimicked by systemic conditions, such as infections, autoimmune disorders, nutritional deficiencies, toxic factors and non-hematological malignancies. However, myelodysplastic syndromes may truly coexist with other systemic diseases, which can be masked when the patient's symptoms are attributed exclusively to myelodysplastic syndromes without further investigation. To better illustrate this, we herein describe two cases associated with synchronous gastric cancers.

https://doi.org/10.1016/j.bjhh.2014.07.005 1102 downloads

12.

PTK2 and PTPN11 expression in myelodysplastic syndromes
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Lazarini, Mariana Machado-Neto, Joao Agostinho Archangelo, Leticia Frohlich Mendes-Silva, Bruna Fernandes Bigarella, Carolina Louzao Traina, Fabiola Saad, Sara Teresinha Olalla

Clinics

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oct 2013, Volume 68 N. 10 Pages 1371 - 1375

Abstract: En | Text: En | PDF: En

OBJECTIVE: The aim of this study was to evaluate the expression of protein tyrosine kinase 2 and protein tyrosine phosphatase non-receptor type 11, which respectively encode focal adhesion kinase protein and src homology 2 domain-containing protein-tyrosine phosphatase 2, in hematopoietic cells from patients with myelodysplastic syndromes. METHODS: Protein tyrosine kinase 2 and tyrosine phosphatase non-receptor type 11 expressions were analyzed by quantitative polymerase chain reaction in bone marrow cells from patients with myelodysplastic syndromes and healthy donors. RESULTS: Protein tyrosine kinase 2 and tyrosine phosphatase non-receptor type 11 expressions did not significantly differ between normal cells and myelodysplastic cells. CONCLUSIONS: Our data suggest that despite the relevance of focal adhesion kinase and src homology 2 domain-containing protein-tyrosine phosphatase 2 in hematopoietic disorders, their mRNA expression do not significantly differ between total bone marrow cells from patients with myelodysplastic syndromes and healthy donors.

https://doi.org/10.6061/clinics/2013(10)13 1530 downloads

13.

Low bone mass density is associated with hemolysis in brazilian patients with sickle cell disease
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Baldanzi, Gabriel Traina, Fabiola Marques Neto, João Francisco Santos, Allan Oliveira Ramos, Celso Dario Saad, Sara T Olalla

Clinics

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2011, Volume 66 N. 5 Pages 801 - 805

Abstract: En | Text: En | PDF: En

OBJECTIVES: To determine whether kidney disease and hemolysis are associated with bone mass density in a population of adult Brazilian patients with sickle cell disease. INTRODUCTION: Bone involvement is a frequent clinical manifestation of sickle cell disease, and it has multiple causes; however, there are few consistent clinical associations between bone involvement and sickle cell disease. METHODS: Patients over 20 years of age with sickle cell disease who were regularly followed at the Hematology and Hemotherapy Center of Campinas, Brazil, were sorted into three groups, including those with normal bone mass density, those with osteopenia, and those with osteoporosis, according to the World Health Organization criteria. The clinical data of the patients were compared using statistical analyses. RESULTS: In total, 65 patients were included in this study: 12 (18.5%) with normal bone mass density, 37 (57%) with osteopenia and 16 (24.5%) with osteoporosis. Overall, 53 patients (81.5%) had bone mass densities below normal standards. Osteopenia and osteoporosis patients had increased lactate dehydrogenase levels and reticulocyte counts compared to patients with normal bone mass density (p<0.05). Osteoporosis patients also had decreased hemoglobin levels (p<0.05). Hemolysis was significantly increased in patients with osteoporosis compared with patients with osteopenia, as indicated by increased lactate dehydrogenase levels and reticulocyte counts as well as decreased hemoglobin levels. Osteoporosis patients were older, with lower glomerular filtration rates than patients with osteopenia. There was no significant difference between the groups with regard to gender, body mass index, serum creatinine levels, estimated creatinine clearance, or microalbuminuria. CONCLUSION: A high prevalence of reduced bone mass density that was associated with hemolysis was found in this population, as indicated by the high lactate dehydrogenase levels, increased reticulocyte counts and low hemoglobin levels.

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14.

Screening for hotspot mutations in PI3K, JAK2, FLT3 and NPM1 in patients with myelodysplastic syndromes
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Machado-Neto, João Agostinho Traina, Fabiola Lazarini, Mariana Campos, Paula de Melo Pagnano, Katia Borgia Barbosa Lorand-Metze, Irene Costa, Fernando Ferreira Saad, Sara T Olalla

Clinics

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2011, Volume 66 N. 5 Pages 793 - 799

Abstract: En | Text: En | PDF: En

INTRODUCTION: Myelodysplastic syndromes encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, refractory cytopenia and a tendency to progress toward acute myeloid leukemia. The accumulation of genetic alterations is closely associated with the progression of myelodysplastic syndromes toward acute myeloid leukemia. OBJECTIVE: To investigate the presence of mutations in the points most frequent for mutations (hotspot mutations) in phosphatidylinositol-3-kinase (PI3K), Janus kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1), which are involved in leukemia and other cancers, in a population of Brazilian MDS patients. METHODS: Fifty-one myelodysplastic syndromes patients were included in the study. According to French-American-British classification, the patients were distributed as follows: 31 with refractory anemia, 8 with refractory anemia with ringed sideroblasts, 7 with refractory anemia with excess blasts, 3 with refractory anemia with excess blasts in transformation and 2 with chronic myelomonocytic leukemia. Bone marrow samples were obtained and screened for the presence of hotspot mutations using analysis based on amplification with the polymerase chain reaction, sequencing, fragment size polymorphisms or restriction enzyme digestion. All patients were screened for mutations at the time of diagnosis, and 5 patients were also screened at the time of disease progression. RESULTS: In the genes studied, no mutations were detected in the patients at the time of diagnosis. One patient with chronic myelomonocytic leukemia was heterozygous for a Janus kinase 2 mutation after disease progression. CONCLUSIONS: These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression.

3632 downloads Cited 1 time in SciELO

15.

Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience
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Pagnano, Kátia Borgia Barbosa Traina, Fabiola Takahashi, Tatiana Oliveira, Gislaine Borba Rossini, Marta Soares Lorand-Metze, Irene Vigorito, Afonso Celso Miranda, Eliana Cristina Martins Souza, Cármino Antonio De

Sao Paulo Medical Journal

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nov 2000, Volume 118 N. 6 Pages 173 - 178

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

CONTEXTO: Pacientes adultos com diagnóstico de leucemia mielóide aguda (LMA) obtém remissão completa (RC) com quimioterapia convencional em cerca de 55-85% dos casos, e a sua duração é de aproximadamente 12 meses. Cerca de 30% dos pacientes não atingem a RC. Para manter a RC e obter cura definitiva parece ser necessário intensificar o tratamento após a RC. No Brasil, há um pequeno número de artigos publicados a esse respeito. OBJETIVO: Descrever a experiência brasileira no tratamento de leucemia mielóide aguda "de novo" em jovens e adultos com idade inferior a 60 anos. TIPO DE ESTUDO: Análise retrospectiva. LOCAL: Hospital das Clínicas e Hemocentro da Universidade Estadual de Campinas. PARTICIPANTES: Foram estudados, retrospectivamente, casos novos de LMA entre 1994 e 1998, com relação à resposta ao tratamento de quimioterapia, sobrevida global e sobrevivência livre de doença. RESULTADOS: Entraram no estudo 78 pacientes de LMA, incluindo 17 casos de leucemia promielocítica (LPM). A média de seguimento foi de 272 dias. A taxa de RC foi de 63,6% nos pacientes com LMA excluindo-se os pacientes com LPM, e 78% nos pacientes com LPM. A sobrevida livre de doença em 5 anos foi de 80% nos pacientes com LPM e 34% para os pacientes com LMA (P=0,01). A sobrevida global foi de 52% e 20,5% para os pacientes com LPM e LMA respectivamente (P=NS). Recidiva foi observada em 12/39 (30,7%) dos pacientes com LMA e 1/11 (9%) na LPM. CONCLUSÕES: Esses resultados são semelhantes aos encontrados na literatura, entretanto, o número de recidivas e a mortalidade mantém-se alta, recomendando-se pesquisa de estratégias mais agressivas para prevenir recidivas.

CONTEXT: Young patients affected by acute myeloid leukemia (AML) achieve complete remission (CR) using conventional chemotherapy in about 55-85%. However, 30% of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML) in younger adult patients (age < 60 years). DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil. PARTICIPANTS: Newly diagnosed cases of "de novo" AML in the period from January 1994 to December 1998 were evaluated retrospectively, in relation to response to treatment, overall survival (OS) and disease free survival (DFS). Cases with acute promyelocytic leukemia (APL) were also included in this analysis. RESULTS: On the basis of an intention to treat, 78 cases of AML, including 17 cases of APL, were evaluated. The overall median follow-up was 272 days. The complete remission (CR) rate was 63.6% in the AML group (excluding APL) and 78% in the APL group. The 5-year estimated disease-free survival (DFS) was 80% for the APL group and 34% for the AML group (P = 0.02). The 5-year estimated overall survival (OS) was 52% for the APL group and 20.5% for the AML group, respectively (P = NS). Relapse was observed in 12/39 (30.7%) patients with AML and 1/11 (9%) with APL. CONCLUSIONS: These results are similar to those reported in the literature. However, relapse and mortality rates remain high, and a search for more aggressive strategies in order to prevent relapse is recommended.

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