Combined Therapy of ATRA and Imatinib Mesylate Decreases BCR-ABL and ABCB1/MDR1 Expression Through Cellular Differentiation in a Chronic Myeloid Leukemia Model.

Background/aim: Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease, and a major challenge for the eradication of CML is to understand the cause of the permanence of minimal residual disease (DRM). This work aimed to induce the maturation of leukemic stem cells with All-trans-retinoic acid (ATRA), making them sensitive to treatment with Imatinib (IM).

Materials And Methods: K562 cells were treated with IM and with the combined therapy of ATRA together with IM for 48 and 72 h.

Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil.

Objectives: To evaluate the effects of epoetin (EPO) alfa treatment on overall survival, event-free survival and response duration in patients with myelodysplastic syndrome (MDS) who were treated at a haematological referral centre in northeastern Brazil.

Methods: This was a retrospective cohort study of 36 patients diagnosed with MDS and treated with EPO alfa at 30,000 to 60,000 IU per week. Clinical data were collected from medical records.

Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

Introduction And Objective: In this study, we evaluated the influence of the transcript type on hematological and clinical parameters, as well as the event-free survival of 50 patients in the Chronic myeloid leukemia chronic phase.

Methods: We reviewed the medical records of 55 patients with Chronic myeloid leukemia. The eligibility criteria were based on the availability of hematological and clinical baseline data in the medical records.

Presence of CD34 in Megakaryocytes in Association With p53 Expression Predicts Unfavorable Prognosis in Low-risk Myelodysplastic Syndrome Patients.

Background/aim: Although risk stratification using the Prognostic Scores Systems (IPSS, WPSS and IPSS-R) incorporate key information about prognosis of patients with Myelodysplastic syndromes (MDS), patients classified as low-risk may evolve rapidly and aggressively, despite a "favorable" prognostic stratification. The aim of this study was to identify biomarkers for predicting prognosis, and for better stratification and management of these patients.

Materials And Methods: Expression of CD34 and p53 in megakaryocytes was examined by immunohistochemistry in 71 MDS patients classified as low-risk.

Wernicke's encephalopathy in a patient with non-Hodgkin's lymphoma post-Autologous HSCT.

Wernick's Encephalopathy (WE) is an acute neuropsychiatric syndrome caused by thiamine deficiency post hematopoietic stem cell transplant (HSCT). WE is associated with high mortality and morbidity rates, but due to its rare occurrence, it is rarely considered in patients submitted to this procedure. Considering that, the manuscript reports the clinical characteristics and the possible factors that predisposed the occurrence of WE in a patient with non-Hodgkin's lymphoma post-Autologous HSCT.

Interleukin-8 and nuclear factor kappa B are increased and positively correlated in myelodysplastic syndrome.

The pathogenesis of myelodysplastic syndromes (MDS) is complex and depends on the interaction between aberrant hematopoietic cells and their microenvironment, probably including aberrations in cytokines and their signaling pathways. To evaluate interleukin-8 (IL-8) plasma levels and nuclear factor kappa B (NF-kB) in patients with MDS and to test possible correlation between IL-8 and NF-Kb, a total of 45 individuals were analyzed: 25 consecutive adult de novo MDS patients and 20 sex and age-matched healthy elderly volunteers. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay.

Presence of new mutations in the TP53 gene in patients with low-risk myelodysplastic syndrome: two case reports.

Background: Myelodysplastic syndromes are heterogeneous disorders. Patients with myelodysplastic syndrome disease often have ineffective hematopoiesis, cytopenias, blood cell dysplasia in one or more cell types, and are at high risk for developing acute myeloid leukemia. In myelodysplastic syndrome, mutations of TP53 gene are usually associated with complex karyotype and confer a worse prognosis.

Association of oxidative stress and DNA damage with grafting time in patients with multiple myeloma and lymphoma submitted to autologous hematopoietic stem cell transplantation.

The aim of the study was to investigate the association between oxidative stress and DNA damage with grafting time in patients submitted to autologous hematopoietic stem-cell transplantation (HSCT). The study included 37 patients submitted to autologous HSCT diagnosed with Multiple Myeloma (MM) and lymphoma (Hodgkin's and non-Hodgkin's). Biomarkers of oxidative stress and DNA damage index (DI) were performed at baseline (pre-CR) of the disease and during the conditioning regimen (CR), one day after the HSCT, ten days after HSCT and twenty days after HSCT, as well as in the control group consisting of 30 healthy individuals.

Relevance of prognostic factors in the decision-making of stem cell transplantation in Myelodysplastic Syndromes.

The hematopoietic stem cell transplantation (HSCT) is the only curative alternative for Myelodysplastic Syndrome (MDS), but many patients are not eligible for this treatment, as there are several limiting factors, especially in the case of patients with low-risk MDS. The aim of this study is to discuss the factors that can guide the decision-making on referring or not a patient to HSCT. Three cases of MDS, two of which were submitted to HSCT are presented.

The Effect of a Selective Inhibitor of Phosphodiesterase-9 on Oxidative Stress, Inflammation and Cytotoxicity in Neutrophils from Patients with Sickle Cell Anaemia.

The aim of the study was to investigate the possible anti-inflammatory and antioxidant effects of BAY 73-6691 on neutrophils from SCA patients. This study included 35 patients with a molecular diagnosis of SCA, whose neutrophils were isolated and treated with BAY 73-6691 at the concentrations 100, 10, 1.0 and 0.

Effect of different doses of zoledronic acid in establishing of bisphosphonate-related osteonecrosis.

Objectives: To establish osteonecrosis of the jaws in rats treated with different doses of zoledronic acid (ZA).

Methods: Male Wistar rats (n=6-7) received three consecutive weekly intravenous ZA infusions at doses of 0.04, 0.

Pattern of hemolysis parameters and association with fetal hemoglobin in sickle cell anemia patients in steady state.

Objective: This study aimed to evaluate the influence of fetal hemoglobin (Hb F) on hemolysis biomarkers in sickle cell anemia patients.

Methods: Fifty adult sickle cell anemia patients were included in the study. All patients were taking hydroxyurea for at least six months and were followed at the outpatient clinic of a hospital in Fortaleza, Ceará, Brazil.

Monocyte chemoatractant protein-1: a potential biomarker of renal lesion and its relation with oxidative status in sickle cell disease.

Background: The aim of this study was to evaluate the monocyte chemoatractant protein-1 (MCP-1) as a novel biomarker of renal lesion in sickle cell disease (SCD) and correlate it with oxidative stress.

Methods: This is a prospective study with SCD patients followed at a tertiary center in Brazil. Urine samples were collected to dosage of protein, MCP-1, malondialdehyde (MDA) and urinary creatinine.

Tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome.

Background: At the time of diagnosis, more than 50% of patients with myelodysplastic syndrome have a normal karyotype and are classified as having a favorable prognosis. However, these patients often show very variable clinical outcomes. Furthermore, current diagnostic tools lack the ability to look at genetic factors beyond karyotyping in order to determine the cause of this variability.

Influence of βS-globin haplotypes and hydroxyurea on tumor necrosis factor-alpha levels in sickle cell anemia.

Background: Sickle cell anemia is a chronic inflammatory disease characterized by an increased production of proinflammatory cytokines including tumor necrosis factor-alpha. Hydroxyurea, by decreasing the polymerization of hemoglobin, reduces inflammatory states. The effect of the genetic polymorphisms of sickle cell patients on tumor necrosis factor-alpha levels remains unknown.

Impact of iron overload on interleukin-10 levels, biochemical parameters and oxidative stress in patients with sickle cell anemia.

Objective: The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients.

Methods: A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15).

The role of iron overload on oxidative stress in sickle cell anemia.

Unlabelled: Repeated blood transfusions in patients with sickle cell anemia (SCA) increases the risk of iron overload (IO), contributing to oxidative stress.

Materials & Methods: Blood samples of 15 SCA patients without IO (group 1) and 15 SCA patients with IO (group 2) and 30 healthy individuals were collected to investigate oxidative stress. IO was categorized using repeated measures of serum ferritin.

Serum concentrations of nitrite and malondialdehyde as markers of oxidative stress in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.

Background: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11) translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression.

Impact of β(S)-globin haplotypes on oxidative stress in patients with sickle cell anemia in steady state.

Background And Aims: In Brazil, sickle cell anemia (SCA) is one of the most common genetic disorders. The levels of fetal hemoglobin (HbF) may be influenced by the presence of genetic modifiers; among these are the β(S)-globin haplotypes, associated with the clinical heterogeneity presented by the disease. Patients with SCA have an imbalance between the production of reactive oxygen species and antioxidant capacity, generating oxidative stress.

DNA damage in leukocytes of sickle cell anemia patients is associated with hydroxyurea therapy and with HBB*S haplotype.

Hydroxyurea (HU) is the primary pharmacologic agent for preventing the complications and improving the quality of life of sickle cell anemia (SCA) patients. Although HU has been associated with an increased risk of leukemia in some patients with myeloproliferative disorders, the mutagenic and carcinogenic potential of HU has not been established. This study used the alkaline comet assay to investigate DNA damage in peripheral blood leukocytes from 41 individuals with SCA treated with HU (SCAHU) and from 26 normal individuals.