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. 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.

Clinical events and their relation to the tumor necrosis factor-alpha and interleukin-10 genotypes in Sickle-Cell-Anemia patients.

OBJECTIVE/BACKGROUND: Sickle-cell anemia (SCA) is a genetic blood disease characterized by chronic inflammation and a heterogeneous clinical picture. Serum tumor necrosis factor (TNF-alpha) and interleukin 10 (IL-10) levels are associated with the clinical course of SCA. This study aimed to evaluate the association between the frequency of the polymorphisms TNF-alpha-308 G→A, IL-10-1082 G→A, IL-10-819 C→T, and IL-10-592 A→C; serum TNF-alpha; and IL-10 levels, and the incidence of clinical events in SCA patients. METHODS: Polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay were performed on 25 adults with SCA at the steady state; their data were compared with those for 26 healthy individuals. RESULTS: The most frequent genotype of the TNF-alpha polymorphism was GG (low producer), and the most frequent genotype of the IL-10 polymorphisms was "low producer" (ACC ACC, ACC ATA, ATA ATA). The TNF-alpha levels were significantly higher in SCA in patients with acute chest syndrome (ACS). The IL-10 levels were reduced in polytransfusion and in patients with ACS. CONCLUSION: The patients presented prevalence of TNF-alpha and IL-10 low-profile producer. The cytokine serum levels presented an association with the presence of polytransfusion and ACS in SCA patients.

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. Patients taking hydroxyurea (SSHU) were compared to those not taking the drug (SS). Patients' data were also compared to a control group of 15 healthy blood donors. RESULTS: MCP-1 dosage was increased in SCD patients (Control: 42.12±27.6; SSHU: 168.2±90.1 and SS: 231.4±123.7 p<0.0001). SS patients presented higher levels of MCP-1 in comparison to SSHU group (SSHU: 168.2±90.10 and SS: 231.4±123.7; p=0.023). The same results were observed for MDA (Control: 2:29±1:13; SSHU: 5.60±2.39 and SS: 7.23±2.64, p<0.0001) and NO (control: 2.25±1.9; SSHU: 56.54±9.1 and SS: 39.1±9.02, p<0.0001). A positive correlation was obtained between MCP-1 and MDA (r=0.34, p=0.01); albuminuria (r=0.5, p=0.03); NO (r=0.39, p=0.005). CONCLUSION: The outcomes of the study suggest that MCP-1 is a predictive biomarker of renal lesion that can also reflect damage caused by oxidative stress present in SCD.

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. The biomarkers evaluated were plasmatic malondialdehyde (MDA), nitrite and erythrocyte catalase. RESULTS: MDA and nitrite were higher in group 2 than in group 1 and the healthy group (p < 0.001 for MDA and nitrite). Catalase presented lower in group 2 than group 1 and the healthy group (p < 0.001). We obtained a positive correlation between ferritin and MDA (r = 0.40; p < 0.02), and between ferritin and nitrite (r = 0359; p = 0.023). CONCLUSION: The results demonstrated that IO is an important risk factor for enhanced oxidative stress in SCA.