Sickle cell disease (SCD) is a hereditary blood disorder caused by a single gene. Various blood and urine biomarkers have been identified in SCD which are associated with laboratory and medical history. Biomarkers have been proven helpful in identifying different interconnected disease-causing mechanisms of SCD, including hypercoagulability, hemolysis, inflammation, oxidative stress, vasculopathy, reperfusion injury and reduced vasodilatory responses in endothelium, to name just a few. However, there exists a need to establish a panel of validated blood and urine biomarkers in SCD. This paper reviews the current contribution of biochemical markers associated with clinical manifestation and identification of sub-phenotypes in SCD.

Nutritional research in sickle cell disease has been the focus in recent times owing to not only specific nutritional deficiencies, but also the improvements associated with less painful episodes. Though hydroxyurea remains the drug of choice, certain adverse health effects on long term supplementation makes room for researches of different compounds. Macro and micro nutrient deficiencies, along with vitamins, play an important role in not only meeting the calorific needs, but also reducing clinical complications and growth abnormalities. Symptoms of hyper protein metabolism, increased cell turnover, increased cardiac output, and appetite suppression due to enhanced cytokine production, might give us leads for better understanding of the mechanisms involved. Different nutritional approaches comprising of traditional herbal therapies, antioxidants, flavonoids, vitamins, minerals etc., reducing oxidative stress and blood aggregation, have been tried out to increase the health potential. Nutritional therapies may also serve complementary to the newer therapies using ozone, hematopoietic stem cell transplantation, antifungal medications, erythropoietin etc. Herein we try to present a holistic picture of the different patho-physiological mechanisms, and nutritional strategies adopted.

To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL.

We report here the spectrum of δ-globin gene mutations found in the UK population. Nine different δ chain variants and two δ-thalassemia (δ-thal) mutations were characterized in a study of 127 alleles in patients with either a low Hb A2 value or a split Hb A2 peak on high performance liquid chromatography (HPLC). The most common δ chain variant was Hb [Formula: see text] (or Hb B2) [δ16(A13)Gly → Arg; HBD: c.49G > C] (77.0%), followed by Hb A2-Yialousa [δ27(B9)Ala → Ser; HBD: c.82G > T] (12.0%), Hb A2-Babinga [δ136(H14)Gly → Asp; HBD: c.410G > A] (3.0%), Hb A2-Troodos [δ116(G18)Arg → Cys; HBD: c.349C > T] (1.0%), Hb A2-Coburg [δ116(G18)Arg → His; HBD: c.350G > A] (2.0%) and Hb A2-Indonesia [δ69(E13)Gly → Arg; HBD: c.208G > C] (1.0%). Three novel variants were identified: Hb A2-Calderdale [codon 2 (CAT > AAT), His → Asn; HBD: c.7C > A], Hb A2-Walsgrave [codon 52 (GAT > CAT), Asp → His; HBD: c.157G > C] and Hb A2-St. George's [codon 81 (CTC > TTC), Leu → Phe; HBD: c.244C > T]. In addition, two known δ-thal mutations were observed: -68 (C > T); HBD: c.-118C > T and codon 4 (ACT > ATT); HBD: c.14C > T. Amplification refractory mutation system (ARMS) primers were developed to provide a simple molecular diagnostic test for the most common variant, Hb [Formula: see text]. Three of the variants had a characteristic HPLC retention time that can be used for a presumptive diagnosis.

No abstract

There remains significant controversy over the techniques used for clonal diagnosis of lymphoproliferative disorders because of questions regarding the sensitivity, specificity and throughput. This has stimulated us to explore the use of gene scan to determine clonality of Immunoglobulin (Ig)/T-cell receptor (TCR) (gamma gene rearrangement in a variety of morphologically, cytochemically, pathologically and immunophenotypically defined precursor B/T-ALL (12 patients), 5 patients with NHL, 10 patients with CLL and a group of reactive lymphocytosis as a reference group (10 subjects). Polymerase chain reaction (PCR) was done for IgH gene (FR3a, FR2b, LJH and JH primers) and for TCR gamma gene and the malignant clone was identified using gene scan (GS) analysis. In the ALL group, monoclonality was detected using GS and using IgH (FR2b) 75% had a clonal band, 63% with IgH (FR3a) and 88% with a combination of FR3a/FR2b. The results of TCR gamma monoclonality were 50% using primer mix I, 25% using primer mix II and 75% using a combination. In the CLL group, clonal IgH gene rearrangement was detected by FR2b in 80% of cases, while by FR3a clonal rearrangement was detected in 60%, the combination of FR2b and FR3a increased the detection rate to 90%. In B-cell NHL, the FR2b was clonally rearranged in 50% while FR3 was positive in 25%. In reactive lymphocytosis, all cases revealed polyclonal rearrangement with TCR gamma primers. The sensitivity and positive predictive value of GS was 100% and the specificity and negative predictive value was 86.6%. In conclusion, gene scanning provides a sensitive and specific method for detection of the malignant clone in PCR product in patients with lymphoproliferative disorders.

The present studydetect the prevalence of cardiac complications and the efficacy of iron overload monitoring by ECHO (LVEF), and serum ferritin assay in patients at Department of Clinical Hematology with β thalassemia major (βTM). Case records of all βTM patients were analyzed for clinical data, age, sex, heart failure, serum ferritin, ECG, chest x-ray and echocardiography. Sixty -two βTM patients with serially recorded LVEF are included in statistical analysis. Age range of these patients was 4-36 years. Clinical congestive cardiac failure (CHF) was observed in 5 patients(6.45%) with the age range of 13-28 years, 34 patients (54.8%) have normal ECHO findings while 28 patients (45.2%) have valvular heart disease, 8 patients (12.6%) had tricuspid regurgitation with pulmonary hypertension, and 20 patients (32.2%) had tricuspid, mitral or aortic regurgitation. The present study indicated that Observation of excess iron in the heart of βTM patients in King Abdulaziz University Hospital (KAUH) through LVEF and serum ferritin analysis have reduced incidence of CHF. LVEF instructs the use of intensive chelation therapy but cannot prevent or predict heart damage or CHF in the course of the disease; this may be due to the poor prognosis once CHF is occurred. More sensitive methods for early detection of cardiac complication arerequired as MRI T2* which is used to estimate myocardial iron and identifies pre-clinical cardiac iron deposition to prevent irreversible cardiac complication.