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Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoiet­ic disorders characterized by ineffective hematopoiesis, cytopenias and dysplasia and one or more lineages. The stratification of MDS is made based on the percentage of bone marrow blasts, number of cytopenias and karyotype at diagnosis. Somatic mutations in the p53 tu­mor suppressor gene are found in approximately 50% of all human tumors, making it the most commonly mutated gene. The expression of p53 protein and the study of mutations is especially needed in the prognosis of MDS. In this context, the study aims to evaluate the expansion of mesenchymal stromal cells (MSCs) and the expression of p53 protein in pa­tients with SMD, low risk, according to the International Prognostic System (IPSS), in order to demonstrate the importance of these evaluations also diagnostics. This is a cross-sectional analytical study with review 3 adult patients of both sexes, the diagnosis of low-risk MDS receiving outpatient treatment at the University Hospital Walter Cantídio (HUWC). MSCs were characterized by immunophenotyping and screening of mutation of the p53 gene by Real Time PCR System (Applied Biosystems). For data analysis, the statistical software was used GraphPadPrism 5.0. Statistical differences between groups were checked by Student t or Mann-Whitney’s test significance level was p < 0.05 for all analyzes. The results showed a smaller expansion of MSCs in the bone marrow of patients with MDS compared with a control group. A survey of mutation of the p53 gene was negative in all patients. The results demonstrate an impairment in the growth of MSCs in patients with MDS, collaborating with the hypothesis that medullary microenvironment in MDS may be compromised contributing greater understanding of disease mechanisms. However studies with larger sample should be conducted in order to establish the best results.

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. Data on BCR-ABL transcripts were obtained from medical records. Results: Eighteen patients (36%) had the b2a2 transcript, 24 (48%) had b3a2 and 8 (16%) had b2a2/b3a2. The median platelet count for transcripts b2a2, b3a2 and b2a2/b3a2 was 320.65 × 103/L, 396 × 103/L, and 327.05 × 103/L, respectively (p = 0.896). We could not find any differences in relation to the other hematological parameters, when compared to the transcript type. Comparison between spleen and liver size and type of transcript did not differ inside the groups (p = 0.395 and p = 0.647, respectively) and the association between risk scores and transcript type did not show statistical significance (p > 0.05). The 21-month probability for event-free survival was 21%, 48% and 66% for the transcripts b2a2, b3a2 and b2a2/b3a2 respectively (p = 0.226) Conclusion: We conclude that the expression BCR-ABL transcripts have no influence on hematological, clinical and event-free survival parameters of patients in the Chronic myeloid leukemia chronic phase. Keywords: Chronic myeloid leukemia, BCR-ABL, Prognosis

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. Results CD34 staining in megakaryocytes was associated with p53 expression (p=0.0166). CD34 and p53 expression were associated to worse overall survival in patients (p=0.0281). Conclusion The presence of CD34 in megakaryocytes is associated with p53 expression and an adverse prognosis for MDS patients.

Introduction: Patients with sickle-cell disease (SCD) present chronic hemolysis with increased serum biomarkers. Genetic polymorphisms of the BLC11A gene modulate fetal hemoglobin (HbF), thus reducing hemolysis Objective: To associate the polymorphisms of BCL11A gene with the hemolysis markers: reticulocyte, bilirubin, uric acid, lactate dehydrogenase (LDH), and methemoglobin (MetHb) in SCD patients. Methods: The study included 45 patients with SCD of both sexes using hydroxyurea (HU), treated at a Hospital in Fortaleza, Ceará, Brazil, along with 80 healthy individuals as the control group. MetHb, uric acid, and bilirubin measurements were carried out with the spectrophotometric method, and LDH with a kinetic method, a reticulocyte count by a manual method; and evaluation of BCL11A polymorphisms, in real time polymerase chain reaction (PCR). Data were analyzed using the statistical software GraphPad Prism. The level of significance was set at < 5%. Results: In region rs7557939 of the BCL11A gene genotype, A/G showed a significant increase of MetHb (p = 0.0297), and the A/A genotype showed high concentration of LDH (p = 0.0316) in the same region. The use of HU at doses ≥ 10 mg/kg/day showed a decrease of LDH (p = 0.02), and treatment for > 50 months was linked to the reticulocyte count (p = 0.0155). Conclusion: Polymorphisms in the rs7557939 region of the BCL11A gene appear to somehow interfere in the clinical setting of patients with SCD, suggesting relation with the concentration of MetHb and LDH. This study pioneered an investigation into the association of hemolysis biomarkers with BCL11A gene polymorphisms in SCD. RESUMO Introdução: Pacientes com anemia falciforme (AF) apresentam hemólise crônica com biomarcadores séricos aumentados. Os polimorfismos genéticos do gene BLC11A modulam a hemoglobina fetal (HbF), reduzindo, assim, a hemólise. Objetivo: Associar os polimorfismos do gene BCL11A aos marcadores de hemólise: reticulócitos, bilirrubina, ácido úrico, lactato desidrogenase (LDH) e meta-hemoglobina (MetHb) em pacientes com AF. Métodos: O estudo incluiu 45 pacientes com AF que utilizavam hidroxiureia (HU), tratados em um hospital de Fortaleza, Ceará, Brasil, e 80 indivíduos saudáveis como grupo-controle. A dosagem de MetHb, ácido úrico e bilirrubina foi realizada por método espectrofotométrico; LDH, pelo método cinético; contagem de reticulócitos, pelo método manual; e avaliação de polimorfismos BCL11A, por reação em cadeia da polimerase (PCR) em tempo real. Os dados foram analisados usando o software estatístico GraphPad Prism. O nível de significância foi < 5%. Resultados: Na região rs7557939 do gene BCL11A, o genótipo A/G mostrou aumento significativo de MetHb (p = 0,0297), e o genótipo A/A esteve relacionado com a alta concentração de LDH (p = 0,0316). Pacientes em uso de HU em doses ≥ 10 mg/kg/dia apresentaram diminuição de LDH (p = 0,02), e o tratamento por mais de 50 meses foi relacionado com a contagem de reticulócitos (p = 0,0155). Conclusão: Polimorfismos na região rs7557939 do gene BCL11A parecem interferir de alguma forma nas manifestações clínicas de pacientes com AF, o que sugere uma relação com a concentração de MetHb e LDH. Este estudo foi pioneiro na investigação da associação de biomarcadores de hemólise com polimorfismos do gene BCL11A na AF.

SUMMARY 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. We conclude that WE should be considered in patients submitted to autologous HSCT associated with prolonged use of TPN and malnutrition.

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. The control group consisted of 20 hemoglobin AA individuals. The reticulocyte count was performed by an automated methodology, lac- tate dehydrogenase and uric acid were measured by spectrophotometry and arginase I by enzyme-linked immunosorbent assay (ELISA). The presence of Hb S was detected by high-performance liquid chromatography. The level of significance was set for a p -value

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. MDS patients showed higher level of IL-8 when compared to controls (p = 0.006). Patients aged 75 and above showed even higher levels (p = 0.035). NF-kB activity was significantly elevated in MDS patients when compared to controls (p

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. In the present study, two mutations in this gene are presented and discussed with the clinical evolution of the patients. Case presentation The first case is a 77-year-old Brazilian woman diagnosed as having multiple lineage dysplasia myelodysplastic syndrome according to World Health Organization 2016 and classified as very low-risk by Revised International Prognostic Scoring. The second case is an 80-year-old Brazilian man also diagnosed as having multiple lineage dysplasia myelodysplastic syndrome and classified as low risk. The mutation described in the first case was already identified in some neoplasias and it is associated with a poor prognosis, but it had never been reported before in myelodysplastic syndrome. The second mutation has never been described. Conclusions This is a novel report for the scientific community and may be very helpful as we can better understand the disease and the impact of mutations through the follow-up of these patients and others in the future. Both patients are in a good clinical condition, suggesting that these mutations may not alter the clinical course of the disease or may be associated with a good prognosis, but their role in the disease must be investigated more deeply in a larger population.

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. Objective To evaluate the impact of p53 protein expression at diagnosis in patients with low-risk myelodysplastic syndrome. Methods This study enrolled 38 patients diagnosed with low-risk myelodysplastic syndrome. Clinical data were collected by reviewing medical records, and immunohistochemical p53 staining was performed on bone marrow biopsies. Results Of the 38 participants, 13 (34.21%) showed p53 expression in their bone marrow. At diagnosis, this group of patients also presented clinical features characteristic of a poor prognosis more often than patients who did not express p53. Furthermore, patients expressing p53 had a shorter median survival time compared to those without p53 expression. Conclusion This study shows that the expression of p53 at diagnosis is a useful indicator of distinct clinical characteristics and laboratory profiles found in low-risk myelodysplastic syndrome patients. These data indicate that the immunohistochemical analysis of p53 may be a prognostic tool for myelodysplastic syndrome and should be used as an auxiliary test to help determine the best therapeutic choice.

The chronic inflammatory state in sickle cell anemia (SCA) is associated with several factors such as the following: endothelial damage; increased production of reactive oxygen species; hemolysis; increased expression of adhesion molecules by leukocytes, erythrocytes, and platelets; and increased production of proinflammatory cytokines. Genetic characteristics affecting the clinical severity of SCA include variations in the hemoglobin F (HbF) level, coexistence of alpha-thalassemia, and the haplotype associated with the HbS gene. The different haplotypes of SCA are Bantu, Benin, Senegal, Cameroon, and Arab-Indian. These haplotypes are associated with ethnic groups and also based on the geographical origin. Studies have shown that the Bantu haplotype is associated with higher incidence of clinical complications than the other haplotypes and is therefore considered to have the worst prognosis. This study aimed to evaluate the profile of the proinflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-17 in patients with SCA and also to assess the haplotypes associated with beta globin cluster S (HBB * S). We analyzed a total of 62 patients who had SCA and had been treated with hydroxyurea; they had received a dose ranging between 15 and 25 (20.0 ± 0.6) mg/kg/day for 6–60 (18 ± 3.4) months; their data were compared with those for 30 normal individuals. The presence of HbS was detected and the haplotypes of the beta S gene cluster were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our study demonstrated that SCA patients have increased inflammatory profile when compared to the healthy individuals. Further, analysis of the association between the haplotypes and inflammatory profile showed that the levels of IL-6 and TNF-α were greater in subjects with the Bantu/Bantu haplotype than in subjects with the Benin/Benin haplotype. The Bantu/Benin haplotype individuals had lower levels of cytokines than those with the Bantu/Bantu haplotype and greater levels than those of subjects with the Benin/Benin haplotype. For IL-17, a slight trend toward decreased levels was observed in the subjects with the Benin/Benin haplotype, when compared to those with the Bantu/Bantu and Bantu/Benin haplotypes; however, this difference was not statistically significant. Our results show that genetic polymorphisms in sickle cell anemia are associated with the inflammatory profile.

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. We intend to report the difficulties in referring patients with MDS to transplant and the prognostic factors that contribute to define eligibility. RESUMO O transplante de células-tronco hematopoéticas (TCTH) é a única alternativa curativa para Síndrome Mielodisplásica (SMD), porém muitos pacientes não são elegíveis para esta opção, pois existem diversos fatores limitantes, principalmente no caso de pacientes com SMD de baixo risco. O objetivo do estudo é discutir os fatores que podem orientar a decisão no encaminhamento ou não para o TCTH. São apresentados três casos de SMD, dos quais dois foram submetidos ao TCTH. Nos propomos a relatar as dificuldades no encaminhamento dos pacientes com SMD ao transplante e os fatores prognósticos que contribuem para definir a elegibilidade.

Introduction.Sickle cell disease (SCD) is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF) concentration. The aim of this study was to evaluate the impact of theβS gene haplotypes and HbF concentration on arginase I levels in SCD patients.Methods.Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. TheβS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed with GraphPad Prism program and the significance level wasp<0.05.Results.Significant increase was observed in the arginase I levels in SCD patients compared to the control group (p<0.0001). The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu×Bantu/Benin groups; Bantu/Bantu×Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed.Conclusion.The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes.

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. The presence of HbS and the analysis of the haplotypes of the beta S gene cluster were done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The damage index (DI) in the SCAHU group was significantly higher than in controls (p0.001). Neither gender nor age was associated with DNA damage in controls or SCAHU individuals. Among the SCAHU individuals, DI was significantly influenced by length of HU treatment (p=0.0039) and BMI (p=0.001). Individuals with length of HU treatment≥20 months and BMI≤20kg/m(2) had a significantly greater DI than those with length of HU treatment20 months and BMI20kg/m(2). No significant influence of mean HU dose was observed on DI (p=0.950). However, individuals who received a mean HU dose≥20mg/kg showed a higher DI than those who received less. Furthermore, an association was observed between DI damage and HBB*S gene haplotypes. DI values for the Bantu/Bantu haplotype was greater when compared to the Benin/Benin haplotype; and the Bantu/Benin haplotype had a DI lower than the Bantu/Bantu haplotype and greater than the Benin/Benin haplotype. Our results show that DNA damage in sickle cell anemia is associated not only with treatment with HU but also with genotype.

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. Nitric oxide (NO) is a potent vasodilator and may be involved in the mechanism of HbF induction. The aim of this study was to evaluate the impact of β S -globin haplotypes in oxidative stress in patients with SCA. Methods The study included 47 patients with SCA in steady state. The molecular diagnosis of SCA and characterization of the β S -globin haplotype was performed by β S chain polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). Concentration of HbF was determined by high-performance liquid chromatography (HPLC). Serum levels of nitrite/nitrate (NOx) and malondialdehyde were determined by spectrophotometry. Results The most prevalent haplotype in the study population was Bantu. The Benin/n group presented significantly higher HbF and nitrite levels as compared to the Bantu/n group. Conclusions Our results confirm data reported in the literature where the Benin and Bantu haplotypes are respectively correlated to high levels and decreased HbF. In addition, haplotypes associated with high levels of HbF showed high levels of nitrite, demonstrating that as the HbF, serum levels of NOx may prove useful as a prognostic biomarker in patients with SCA.

Sir,Since upper gastrointestinal bleeding (UGIB) remains a common condition worldwide, efforts are being continuously made to optimize its management and to improve patients’ outcomes. Latest guide...

Myelodysplastic syndrome (MDS) is a heterogeneous group of stem cell clonal alterations, culminating in a high risk of progression to acute myeloid leukaemia (AML) (Greenberg et al, 2012). The prognosis of these patients is commonly determined by the International Prognostic Score System (IPSS), which considers the number of cytopenias, cytogenetic alterations and number of blasts in the bone marrow at diagnosis. Patients with a lower risk of progression to AML are classified as low risk; however, a subgroup of these patients develops a disease with an aggressive course and a lower survival rate (Mittelman et al, 2010). This clinical heterogeneity reinforces the need to identify auxiliary markers for prognostic stratification systems.

To establish osteonecrosis of the jaws in rats treated with different doses of zoledronic acid (ZA).Male Wistar rats (n=6-7) received three consecutive weekly intravenous ZA infusions at doses of 0.04, 0.20 or 1.00mg/kg ZA or saline (control). Four weeks after the last administration, the animals were submitted to simple extraction of the lower left first molar. An additional dose of ZA was administered seven days later, and the animals were sacrificed 28 days after exodontia. Weight was measured and blood was collected weekly for analysis. The jaw was radiographically and microscopically examined along with the liver, spleen, kidney and stomach.All ZA doses showed a higher radiolucent area than the control (p0.0001), but the dose of 0.04mg/kg did not show BRONJ. Doses of 0.20 and 1.00mg/kg ZA showed histological evidence of bone necrosis (p=0.0004). Anaemia (p0.0001, r(2)=0.8073) and leucocytosis (p0.0001, r(2)=0.9699) are seen with an increase of lymphocytes (p0.0001, r(2)=0.6431) and neutrophils and monocytes (p=0.0218, r(2)=0.8724) in all the animals treated with an increasing dose of ZA. Haemorrhage and ectasia were observed in the spleen (p=0.0004) and stomach (p=0.0168) in a dose-dependent manner, and the animals treated with ZA showed a lower rate of weight gain (p0.0001).We designed a bisphosphonate-related osteonecrosis of the jaw model that reproduces radiographic and histological parameters and mimics clinical alterations such as leucocytosis, anaemia and idiosyncratic inflammatory post infusion reactions.

Introduction: Hemoglobin S (HbS) is unstable hemoglobin that easily oxidizes, causing methemoglobin (MetHb) increased production in patients with sickle-cell anemia (SCA). Objectives: To determine MetHb levels and the influence of hydroxyurea (HU) therapy on this marker in patients with SCA. Materials and methods: Blood samples from 53 patients with SCA at the steady-state, with and without HU therapy, and 30 healthy individuals were collected to evaluate MetHb levels. The MetHb measurement was performed by spectrophotometry. Complete blood count, HU measurements, and fetal hemoglobin (HbF) and HbS concentrations were taken from medical records. Results: MetHb levels were statically higher in patients with SCA when compared to control group (p < 0.001). There was no statistical difference in MetHb level between SCA patients, either using or not HU. We obtained a positive correlation between MetHb measurements and HbS concentration (r = 0.2557; p = 0.0323). Conclusion: HbS presence favored hemoglobin breaking down, and consequently increased MetHb production. Treatment with HU, however, did not influence the levels of this marker. Introdução: A hemoglobina S (HbS) é uma hemoglobina instável que facilmente se oxida, causando aumento da produção de metemoglobina (MetHb) em pacientes com anemia falciforme (AF). Objetivos: Determinar os níveis de MetHb e verificar a influência do tratamento com a hidroxiureia (HU) sobre as dosagens desse marcador em pacientes com AF. Materiais e métodos: Amostras de sangue de 53 pacientes adultos com AF em estado basal, em uso ou não de HU, e 30 indivíduos saudáveis foram coletadas para avaliar os níveis de MetHb. A dosagem de MetHb foi realizada pelo método espectrofotométrico. Os parâmetros hematológicos, a dosagem de HU e a concentração de hemoglobina F (HbF) e HbS foram retirados dos prontuários médicos. Resultados: Níveis de MetHb apresentaram-se mais elevados estatisticamente em pacientes com AF em relação ao grupo-controle (p < 0,0001). Não foi verificada diferença estatística nos níveis de MetHb entre pacientes em uso ou não de HU. Observou-se correlação positiva entre as dosagens de MetHb e a concentração de HbS (r = 0,2557; p = 0,0323). Conclusão: A presença da HbS favoreceu a degradação da hemoglobina, causando elevação da produção de MetHb. Tratamento com HU, entretanto, não influenciou nos níveis desse marcador.

Myelodysplastic syndromes (MDS) are group of stem cell disorders characterised by peripheral cytopaenias and a variable risk of progression to acute myeloid leukaemia. Most patients have anaemia and many develop transfusion dependence and iron overload (IOL), considered to be a negative independent prognostic factor associated with a higher risk of leukemic transformation and shorter survival.1 Iron pool is regarded as an important regulator of the production of reactive oxygen species (ROS). The excessive production of ROS and reactive nitrogen species causes lipid peroxidation, which can suppress self-renewal, the number of haematopoietic stem cells and directly induce DNA damage and genomic instability.2 However, the role of iron-mediated oxidative stress in the physiopathology of MDS remains uncertain. The present study aimed to evaluate plasma nitrite (NO2 −) and plasma malonaldehyde, secondary product of lipid peroxidation, in patients with MDS and correlate them with IOL due to transfusion dependence in MDS patients. Consecutive adult patients with MDS with and without IOL, followed at the University Hospital of the Federal University of Ceara, Brazil, were enrolled. The study was approved by the local ethics committee (licence 150/2009). They were classified according to the presence or absence of IOL defined as serum ferritin of 1000 ng/ml or …

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). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. RESULTS: Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. CONCLUSION: The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia.

Idiopathic cytopenia of undetermined significance (ICUS) is characterized as less than 10% of dysplasias with less than 5% blasts in the bone marrow, however, it may be present heterogeneously. Until the present, only a small number of cases have been published and knowledge about the mechanisms and prognosis is scarce(1). Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems, including the bone marrow(2). Data on changes in the bone marrow in patients with SLE are scarce and inconsistent, but mainly involve hypoplasia, hyperplasia, vasculitis, lymphocytosis/plasmacytosis, myelofibrosis, pure red cell aplasia and dyserythropoiesis. Dysplastic changes in all hematopoietic lineages and peripheral cytopenias have also been described in SLE patients; however, they seem to be reversible with remission of the disease(2,3). Figure 1 illustrates a case of one 18-year-old female patient with persistent refractory cytopenia and mild dysplasia in the three hematopoietic lineages compatible with ICUS. After three years of follow up she was strongly positive for antinuclear antibodies and evolved with glomerulonephritis, characterizing SLE. Figures 2A & B illustrate the cytogenetic analysis with karyotyping by G-band and Fluorescence in situ Hybridization (FISH) for 5q- negative.

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. OBJETIVE: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará. METHODS: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses. RESULTS: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib. Conclusion: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.

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. Objective The aim of this study was to investigate the association of tumor necrosis factor-alpha levels with β-globin haplotypes and the use of hydroxyurea. Methods A cross-sectional study was performed of 67 patients with sickle cell anemia diagnosed at steady-state in a referral hospital in Fortaleza, Ceará, Brazil. A group of 26 healthy individuals was used as control. βS haplotype analysis was performed by restriction fragment length polymorphism-polymerase chain reaction. The tumor necrosis factor- alpha levels were measured by the enzyme-linked immunosorbent assay test. Laboratory data (complete blood count and fetal hemoglobin) and information regarding the use of hydroxyurea were obtained from medical records. Statistical analysis was performed using R software with the Kruskal-Wallis and Mann–Whitney tests. Statistical significance was established for p-values