Eduardo M Rego

• MD, PhD
• Professor (Full) at University of São Paulo

Objective This study aimed to determine the frequency of genetic alterations as deletions and duplications in cytochrome P450 (CYP450) and glutathione S-transferases (GST) genes, as well as to investigate whether there is a relationship between these alterations and neutrophilic hematologic recovery in adult patients diagnosed with acute myeloid le...

Gliomas, particularly glioblastomas, are highly aggressive cancers with rapid proliferation and poor prognosis. Current treatments have limited efficacy, highlighting the need for new therapeutic strategies. Eribulin mesylate, a synthetic macrocyclic ketone, has shown potential as an anticancer agent in several malignancies. This study investigates...

Introduction Bronchoscopy is frequently performed in the management of patients with acute leukemia due to their high susceptibility to infections. In this setting, it is performed in the context of lung infiltrates on imaging and persistent fever in immunocompromised subjects. This study aimed to evaluate the utility of bronchoscopy in patients wi...

Acute myeloid leukemia (AML) with FLT3-ITD mutation represents a quarter of AML patients and is associated with high relapse rate and dismal prognosis. FLT3 tyrosine kinase inhibitors (TKIs) were developed in order to target this genetic alteration and among these TKIs, AC220 (quizartinib) combined with chemotherapy has already shown an increased o...

Ezrin (EZR) is an actin-associated protein that is often upregulated in cancers. Here we investigate the role of EZR in acute lymphoblastic leukemia (ALL) and explore the therapeutic potential of a pharmacological EZR inhibitor, NSC305787. ALL patient cohorts exhibit significantly elevated EZR mRNA levels, indicating its association with the malign...

Background: Cancer therapy-related cardiac dysfunction frequently occurs in patients receiving anthracycline. Ivabradine reduces the heart rate without affecting contractility and has shown anti-inflammatory, antioxidant, and antiapoptotic effects in experimental models of cardiotoxicity. This study aims to evaluate the effect of ivabradine on canc...

The central role of the control of apoptosis in the pathophysiology of Philadelphia chromosome-negative myeloproliferative neoplasms has recently been reinforced in genetic and pharmacological studies. The inhibitor of apoptosis protein family has eight members and plays an important role in apoptosis, with the most studied being survivin (BIRC5) a...

Improvements in clinical assessment have occurred since the last published recommendations on the diagnosis and treatment of acute promyelocytic leukemia in 2013. Here, a committee of specialists of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy presents a comprehensive review on the current knowledge, focusing on the adv...

Despite advancements in utilizing genetic markers to enhance acute myeloid leukaemia (AML) outcome prediction, significant disease heterogeneity persists, hindering clinical management. To refine survival predictions, we assessed the transcriptome of non‐acute promyelocytic leukaemia chemotherapy‐treated AML patients from five cohorts (n = 975). Th...

Background Acute myeloid leukaemia (AML) is considered a costly disease. Depending on the risk stratification, the patient may receive consolidation with cycles of intermediate doses of cytarabine, auto-HSCT or allo-HSCT according to availability in each service and the availability of a compatible donor. Literature data indicate that safety and ef...

Acute 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...

Recent studies have indicated that more than half of adult patients newly diagnosed with Ph+ ALL can now achieve a cure. However, determining the most suitable protocol for less-resourced settings can be challenging. In these situations, we must consider the potential for treatment toxicity and limited access to newer agents and alloSCT facilities....

Myeloid neoplasms result from molecular alterations in hematopoietic stem cells, with acute myeloid leukemia (AML) being one of the most aggressive and with a poor prognosis. Hematopoietic cell kinase (HCK) is a proto-oncogene that encodes a protein-tyrosine kinase of the Scr family, and it is highly expressed in AML. The present study investigated...

Phosphatidylinositol-5-phosphate 4-kinase type 2 (PIP4K2) protein family members (PIP4K2A, PIP4K2B, and PIP4K2C) participate in the generation of PIP4,5P2, which acts as a secondary messenger in signal transduction, a substrate for metabolic processes, and has structural functions. In patients with acute myeloid leukemia (AML), high PIP4K2A and PIP...

Introduction T-cell acute lymphoblastic leukemia (T-ALL) constitutes around 25% of all newly diagnosed cases of acute lymphoblastic leukemia (ALL) in adults. While most pediatric treatment protocols categorize patients (pts) based on their phenotype, this approach is seldom applied to adults. Nevertheless, there is a scarcity of reported cohorts sp...

Introduction and aims: Proteins of the PIP4K2s family (PIP4K2A, PIP4K2B and PIP4K2C) participate in the generation of PIP 4,5P 2 (PIP 2), which acts as a secondary messenger in signal transduction, substrate for metabolic processes or has structural functions. In patients with AML, high expression of PIP4K2A and PIP4K2C is an independent marker of...

Background: Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is a well-established prognostic marker in acute myeloid leukemia (AML), whereas the impact of mutations in the Tirosine-Kinase Domain (TKD) is controversial. The association of TK inhibitors (TKIs) with intensive chemotherapy improved the overall survival (OS) of FLT3-mu...

Introduction. Acute lymphoblastic leukemia (ALL) frequently affects mainly children and young adults. ALL has seen important progresses in diagnosis techniques and treatment approaches in the last decade. However, in some developing countries, there are inequalities in ALL management, such as heterogeneous access to diagnosis technologies (e.g., cy...

Adult patients with Acute Myeloid Leukemia (AML) are stratified according to clinical and laboratory features at diagnosis into favorable-, intermediate-, or unfavorable-risk groups and may be treated differently according to risk. The European LeukemiaNet panel of experts' recommendation for the post-induction treatment of the favorable subgroup i...

Mutations in TP53 ( TP53mut) are present in roughly 10% of acute myeloid leukemia (AML) patients and represent a unique subgroup of patients with very poor prognosis. While the exact mechanisms of TP53mut-driven leukemogenesis remain elusive, transcriptional changes associated with suppression of the TP53 signaling pathway are considered to confer...

Background: The outcome of the treatment for acute myeloid leukemia (AML) in low- and middle-income countries (LMIC) is significantly worse than in high-income ones due to several factors, including higher non-relapse mortality from infections and limited access to hematopoietic stem-cell transplantation (HSCT). In this resource-constrained setting...

Introduction and aims: Adult acute lymphoblastic leukemia (ALL) is a heterogeneous group of highly aggressive hematological malignancies with high recurrence rates and poor prognosis. Pharmacological inhibition of proteins of the phosphatidylinositol-5-phosphate 4-kinase type 2 family (PIP4K2s), through the compound THZ-P1-2, exhibits antileukemic...

Acute myeloid leukemia (AML) is a heterogeneous disease, which remains difficult to treat due to its heterogeneous nature. Recently, metabolic adaptation has been recognized as a trademark of leukemogenesis. Notably, altered function of mitochondria (mt) in leukemic stem cells (LSCs) has been linked to chemoresistance in some patients, causing rela...

The combination of the BCL2 inhibitor venetoclax (VEN) with hypomethylating agents (e.g. azacytidine, AZA) significantly increased complete remission (CR) rates and prolonged overall survival of adults with Acute Myeloid Leukemia (AML) who were ineligible to intensive chemotherapy. However, VEN+AZA is not a curative treatment and resistance to VEN...

Introduction. Acute myeloid leukemia (AML) is the most frequent leukemia among adults and representing 90% of all cases of acute leukemia in adults. Differences in incidence and burden of AML among regions of the world have been reported. When compared with registries from the US, UK and Sweden, Latin-America (LA) AML has a younger age at diagnosis...

Introduction 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 AM...

Simple Summary Pancreatic cancer is one of the most lethal human neoplasms, and its therapeutic repertoire remains limited. Advances in understanding the molecular complexity involved in the biology of the disease have paved the way for new therapeutic opportunities. AD80 is a multikinase inhibitor that inhibits S6K as well as RET, RAF, and SRC and...

Background Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries. Methods Here, we characterized two...

Introduction Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the Philadelphia (Ph) chromosome. After the introduction of imatinib mesylate (IM) in 2000, the natural history of the disease changed. Data on the treatment of CML with IM are from randomized clinical trials. Establishing whether these results can...

Attempts to convert a tumor supportive M2-polarized macrophage microenvironment into a tumor suppressive M1-polarized one have recently received considerable attention. However, the specificity of novel compounds, their mode-of-action, and efficacy on presumed target cells in vivo needs to be interpreted with caution.

Titanium (Ti) nanotopography modulates the osteogenic response to exogenous bone morphogenetic protein 7 (BMP-7) in vitro, supporting enhanced alkaline phosphatase mRNA expression and activity, as well as higher osteopontin (OPN) mRNA and protein levels. As the biological effects of OPN protein are modulated by its proteolytic cleavage by serum pro...

Several laboratory and clinical variables have been reported to be associated with the outcome of intensive chemotherapy for acute myeloid leukemia (AML), but only a few have been tested in the context of hematopoietic stem cell transplant (HSCT). This study aimed to identify genes whose expression of AML at diagnosis were associated with survival...

Background Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries. Methods Here, we characterized two...

The 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 tr...

Aims Despite the development of therapeutic strategies for chronic lymphocytic leukemia (CLL), most patients remain incurable, relapse, or refractory to current treatments, indicating the need to expand the antineoplastic repertoire for this disease. Ezrin (EZR) is a known oncogene in solid tumors and plays a key role in cell survival and BCR-media...

Objetivos A asparagina é um aminoácido não essencial com participação no metabolismo e divisão celular. A asparaginase (L-Asp) é uma enzima com potencial antitumoral porque reduz a asparagina sintetizada pelas células leucêmicas, sendo utilizada nos protocolos pediátricos de leucemia linfoblástica aguda (LLA). No entanto, a L-Asp é associada a even...

Apesar do desenvolvimento de estratégias terapêuticas para a leucemia linfocítica crônica (LLC), a maioria dos pacientes permanece limitadas. Ezrina (EZR) é um oncogene conhecido em tumores sólidos, mas seu papel em neoplasias hematológicas ainda é pouco explorado. Há evidências de que EZR desempenha uma função chave na sobrevivência celular e na a...

Background Even with advances in understanding the physiopathology of Acute Myeloid Leukemia (AML), most patients still relapse leading to poor long-term prognosis and cure rates. Natural Killer (NK) cells are regulated by opposing signals from receptors that activate and inhibit effector function and are known to mediate anti-leukemic immunosurvei...

No contexto da via SLIT-ROBO, estudos sugerem que as funções das moléculas SLIT1 e SLIT2 são semelhantes tanto em processos fisiológicos quanto no contexto do câncer. Sabe-se ainda que a região promotora de ambos os genes se encontra frequentemente hipermetilada em diferentes tipos de neoplasias. Dentro desse contexto, em leucemia mieloide aguda (L...

Introduction Telomeric repeat-containing RNA (TERRA) are long non-coding RNAs transcribed from subtelomeric regions towards telomere ends. TERRA binds to subtelomeric and telomeric regions, forming R-loops, structures composed of DNA-RNA hybrids and displaced single-stranded DNA. TERRA R-loops protect telomeres from DNA damage and promote telomere...

Introdução As neoplasias de diferenciação plasmablástica são doenças hematológicas raras e de apresentação agressiva. Mieloma Plasmablástico (MPL) e Linfoma Plasmablástico (LPB) são dois dos subtipos possíveis, e como podem ter perfis morfológicos e imunofenotípicos idênticos, a diferenciação diagnóstica pode ser difícil. Objetivos Relato de caso...

A Leucemia Mieloide Aguda (LMA) com inv(3)(q21.3q26⋅2) ou t(3;3)(q21.3;q26⋅2)/GATA2, MECOM(EVI1) recebe da Organização Mundial da Saúde classificação diferencial como um dos subtipos raros de LMA com anormalidades genéticas recorrentes e resulta em ativação do gene EVI1 e haploinsuficiência do GATA2. A superexpressão de EVI1 pode ocorrer em associa...

Objetivos A neoplasia de células dendríticas plasmocitóides blásticas (BPDCN) é uma malignidade hematológica rara e agressiva manifestando-se com lesões cutâneas com ou sem envolvimento da medula óssea e disseminação leucêmica. A incidência de infiltração do sistema nervoso central é em torno de 11%. O seu diagnóstico requer biópsia e avaliação mor...

Introduction Methotrexate is an antifolate that has been an essential part of chemotherapy regimens for acute lymphoblastic leukemia (ALL) and specific subtypes of non-Hodgkin lymphoma (NHL), when it is used in high-dose (HD, ≥ 1 g/m2) to overcome the blood-brain barrier. Nephrotoxicity is the major toxicity of HDMTX, possibly inducing critical org...

Introdução A incorporação da asparaginase nos protocolos de tratamento da leucemia linfoblástica aguda (LLA) em adultos parece melhorar os desfechos a longo prazo. Na última década, a forma peguilada da droga (PEG) tornou-se a formulação padrão mais utilizada. No Brasil, a PEG foi incorporada há 5 anos, trazendo consigo um perfil de toxicidade espe...

Objective Venetoclax, a selective inhibitor of BCL2, has been introduced in clinical practice for the treatment of patients with acute myeloid leukemia (AML). PIP4K2s comprise a family of lipid kinases responsible to produce phosphoinositides (PtdIns4,5P2) with structural and signal transduction functions. The combined expression of PIP4K2A and PIP...

Introdução Identificar eventos primários que iniciam e sustentam a proliferação de células-tronco leucêmicas é essencial para escolha de abordagens terapêuticas na Leucemia Mieloide Aguda (LMA). Além de serem identificadas ao diagnóstico, as Células Progenitoras Leucêmicas (CPLs) indicam persistência da doença, sugerindo que sua presença na medula...

Objetivos A Leucemia Mieloide Aguda (LMA) é uma neoplasia hematológica maligna que se origina a partir de mutações nas células tronco hematopoiéticas e que afeta os precursores da linhagem mieloide. Apesar dos avanços no entendimento de sua fisiopatologia, novas opções terapêuticas ainda são necessárias, devido as altas taxas de resistência e recaí...

Introdução Leucemia basofílica aguda é subtipo raro de leucemia aguda e corresponde a menos de 1% dos casos. Em geral surge a partir de doença preexistente, como leucemia mieloide crônica (LMC). Predominam as manifestações clínicas histaminérgicas secundárias a degranulação de basófilos como rash cutâneo, úlceras pépticas e anafilaxia. Objetivos R...

Patients diagnosed with acute lymphoblastic leukemia (ALL) bearing t(4;11)/MLL-AF4 have aggressive clinical features, poor prognosis and there is an urgent need for new therapies to improve outcomes. Panobinostat (LBH589) has been identified as a potential therapeutic agent for ALL with t(4;11) and studies suggest that the antineoplastic effects ar...

In cancer, tumor cells and their neoplastic microenvironment can sculpt the immunogenic phenotype of a developing tumor. In this context, natural killer (NK) cells are subtypes of lymphocytes of the innate immune system recognized for their potential to eliminate neoplastic cells, not only through direct cytolytic activity but also by favoring the...

Introdução A neutropenia febril é a principal complicação infecciosa no paciente com câncer, atingindo 80% dos pacientes hematológicos em quimioterapia. As bactérias gram negativas que colonizam trato gastro-intestinal, como E. coli e K. pneumonie, são as mais encontradas e emergem com resistência a vários antimicrobianos, sendo associadas a alta m...

Treatment of acute leukemia is challenging due to genetic heterogeneity between and even within patients. Leukemic stem cells (LSCs) are relatively drug-resistant and frequently lead to relapse. Their plasticity and capacity to adapt to extracellular stress, in which mitochondrial metabolism and autophagy play important roles, further complicates t...

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are characterized by risk of relapses, poor survival, unwanted side effects and high toxicity with the current therapies. In light of these facts, there are efforts to develop new drugs specific for deregulated molecules that participate in leukemia pathogenesis. Hematopoietic cell ki...

Background: Myeloproliferative neoplasms (MPN) are disorders characterized by an alteration at the hematopoietic stem cell (HSC) level, where the JAK2 mutation is the most common genetic alteration found in classic MPN (polycythemia vera, essential thrombocythemia, and primary myelofibrosis). We and others previously demonstrated that metformin re...

Simple Summary CAR-T cells are genetically modified T cells that are reprogrammed to specifically eliminate cancer cells. Due to its clinical success to treat certain hematological malignancies, novel approaches to improve CAR-T cell-based therapies are being explored. This systematic review gives a worldwide overview of clinical trials evaluating...

While it is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones, the tumor microenvironment (TME) in acute myeloid leukemias (AML) remains poorly understood. Here, we uncover the functional and prognostic relevance of an M2-polarized macrophage compartment. Intra bone marrow co-injection of M2d-macrophage...

Stathmin 1 (STMN1) is a microtubule-destabilizing protein highly expressed in hematological malignancies and involved in proliferation and differentiation. Although a previous study found that the PML–RARα fusion protein, which contributes to the pathophysiology of acute promyelocytic leukemia (APL), positively regulates STMN1 at the transcription...