New Born Screening of Hemoglobinopathies in a Center Tunisian Population.

Sickle cell diseases, β-thalassemia, and other hemoglobinopathies are common in Africa. Their distribution differs from one region to another. There are higher frequencies in Western and Northern Africa.

Immunity in the Progeroid Model of Cockayne Syndrome: Biomarkers of Pathological Aging.

Cockayne syndrome (CS) is a rare autosomal recessive disorder that affects the DNA repair process. It is a progeroid syndrome predisposing patients to accelerated aging and to increased susceptibility to respiratory infections. Here, we studied the immune status of CS patients to determine potential biomarkers associated with pathological aging.

Identification of High-Risk Single Nucleotide Polymorphisms in the Human CYB5R3 Gene Responsible for Recessive Congenital Methemoglobinemia: A Computational Approach.

Introduction: NADH-cytochrome b5 reductase deficiency due to pathogenic variants in the CYB5R3 gene causes recessive congenital methemoglobinemia (RCM) type I or type II. In type I, cyanosis from birth is the only major symptom, and the enzyme deficiency is restricted only to erythrocytes. Whereas in type II, cyanosis is associated with severe neurological manifestations, and the enzyme deficiency is generalized to all tissues.

Emotional and behavioral attitudes of Tunisian youth towards childhood leukemia: health education and primary prevention in perspective.

Background: Given the increasing blood cancer incidence in Tunisia and recent discoveries proving the involvement of environmental factors, this study examined the environmental health literacy (EHL) of Tunisian secondary school students concerning not only this disease, but also their emotional and behavioral attitudes towards leukemia risks.

Methods: A cross-sectional survey was conducted among Tunisian youths (N = 372, 16-20 years; 68% females, 32% males). Data collection took place in four representative public secondary schools in the North, Center, and South of Tunisia.

Molecular characterization of a novel homozygous deletion in β-globin cluster causing (δβ)-Thalassemia among Tunisian family.

Background: Deletions in the β-globin cluster are uncommon and cause thalassemia (thal) with hereditary persistence of fetal hemoglobin. They constitute a heterogenous group of disorders characterized by absent or reduced synthesis of adult hemoglobin (Hb A) and increased synthesis of fetal hemoglobin (Hb F). Although the clinical severity of these disorders are asymptomatic owing to the increased Hb F levels, the molecular basis is very heterogenous due to the large deletions in the β-globin cluster spanning both and genes.

Tyrosol Derivatives, Bearing 3,5-Disubstituted Isoxazole and 1,4-Disubstituted Triazole, as Potential Antileukemia Agents by Promoting Apoptosis.

In the present study, we assess tyrosol derivatives bearing 3,5-disubstituted isoxazoles and 1,4-disubstituted triazoles for their ability to inhibit the proliferation of K562 cells derived from leukemia as well as primary chronic myeloid leukemia (CML) cells obtained from the peripheral blood of 15 CML patients including 10 patients with untreated chronic phase and 5 patients with resistance against imatinib or multiple TKI. Our results showed that most derivatives displayed significant anti-proliferative activity against K562 cells in a dose-dependent manner. Among them, compounds and exhibited greater potent anticancer activity with respective IC values of 16 and 18 µg/mL (45 µM and 61 µM).

Hematological relevance of JAK2 V617F and calreticulin mutations in Tunisian patients with essential thrombocythemia.

Background: The genetic investigation of essential thrombocythemia(ET) has highlighted the presence of driver mutations in ET. Janus kinase JAK2V617F and calreticulin(CALR) mutations are the most frequent driver mutations and have significantly improved the molecular diagnosis of ET. The impact of genetic heterogeneity on clinical features has not been fully elucidated.

Coinheritance of HbO Arab/β0-thalassemia with Severe Manifestation in Newborn.

Objective: In this study, we report a Tunisian newborn boy referred for neonatal hemolytic anemia with yellowish skin and enlarged spleen due to coinheritance of hemoglobin O (HbO) Arab and β-thalassemia.

Study Design: Hematological parameters were collected using an automated blood cell counter. The amounts of Hb fractions were measured by capillary electrophoresis of Hb.

Enhanced Eryptosis in Glucose-6-Phosphate Dehydrogenase Deficiency.

Background/aims: Defects in the Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme enhance cellular oxidative damage, thus impairing erythrocytes and radically shortening their lifespan. We aimed to study programmed erythrocyte cell death in G6PD-deficient patients, describe the molecular genetics basis of G6PD and investigate phenotype-genotype correlations.

Methods: We explored eryptosis using the annexin V-binding assay, taken as an indicator of PS exposure at the erythrocyte surface.

p.(V617F) mutation in Tunisian myeloproliferative neoplasms and its genotype-phenotype correlation.

Myeloproliferative neoplasms (MPNs) comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The relationship between JAK2 p.(V617F) mutation and MPNs was first described in 2005.

Biochemical, Cellular, and Proteomic Characterization of Hereditary Spherocytosis Among Tunisians.

Background/aims: Hereditary Spherocytosis (HS) is the most common erythrocyte membrane disorder causing hemolytic anemia. The wide heterogeneity of both clinical and laboratory manifestations of HS contributes to difficulties associated with the diagnosis of this disorder. Although massive data previously reported worldwide, there is yet no data on HS among the Tunisian population.

First Observation of HbM-Saskatoon at the Origin of Neonatal Cyanosis in a Tunisian Baby.

Several causes are known to be at the origin of neonatal cyanosis among them methemoglobinemia is by inheritance of an hemoglobin (Hb) M variant. This is a rare condition never been reported in Tunisia so far. Here, we report a Tunisian newborn with refractory cyanosis since birth.

Novel mutations in Uridyl-diphosphate-glucuronosyl-transferase 1A1 (UGT1A1) gene in Tunisian patients with unconjugated hyperbilirubinemia.

Introduction: Unconjugated hyperbilirubinemia (UCB) is a feature of Gilbert's syndrome (GS) and Crigler-Najjar's syndrome (CNS), which are two hereditary defects in bilirubin metabolism. Both syndromes are linked to mutations in the UGT1A1 gene, which cause either the decrease or the absence of the UGT1A1 enzymatic activity. Here, we investigated the molecular basis of the UGT1A1 gene in Tunisian patients presenting with unconjugated hyperbilirubinemia.

Tunisian Newborn's Cord Blood: Reference Values of Complete Blood Count and Hemoglobin Fractions.

Objective: This study was aimed to establish local reference values for hematological indices and hemoglobin (Hb) fractions in umbilical cord blood (UCB) for the northern population of Tunisia.

Study Design: Our study included full-term newborns by vaginal deliveries. Hematological parameters were collected using an automated blood cell counter.

EZH2, new diagnosis and prognosis marker in acute myeloid leukemia patients.

Purpose: Acute myeloid leukemia (AML) is a heterogeneous disease. The discovery of novel discriminative biomarkers remains of utmost value for improving outcome predictions. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase of H3K27me3.

Molecular monitoring of Tunisian patients with chronic myeloid leukemia.

Background: bcr-abl fusion gene is the hallmark of chronic myeloid leukemia (CML). RQ-PCR provides an accurate measure of the total leukemia cell mass and the degree to which bcr-abl transcripts are reduced by therapy correlates with progression free survival.

Aim: We report molecular assessment of residual disease in CML Tunisian patients.

Chronic myeloid leukemia patients in Tunisia: epidemiology and outcome in the imatinib era (a multicentric experience).

Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology.

Molecular study of ABCB1 gene and its correlation with imatinib response in chronic myeloid leukemia.

Purpose: The introduction and success of imatinib mesylate have become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, despite its high efficiency, resistance to imatinib has emerged as a significant problem, which may in part be caused by pharmacogenetic variability. Three single-nucleotide polymorphisms (C1236T, G2677T/A, C3435T) and/or mRNA expression changes of ABCB1 gene were demonstrated to be associated with inter-individual variability of imatinib response in CML patients.

hOCT1 gene expression predict for optimal response to Imatinib in Tunisian patients with chronic myeloid leukemia.

Purpose: Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells.

Downregulation of miR-451 in Tunisian chronic myeloid leukemia patients: potential implication in imatinib resistance.

Objectives: Resistance to imatinib has been recognized as a major challenge for the treatment of chronic myeloid leukemia (CML). Aberrant expression of miR-451 has been reported to participate in anticancer drug resistance. However, the role of miR-451 in imatinib resistance has not been investigated.

Regulatory network analysis of microRNAs and genes in imatinib-resistant chronic myeloid leukemia.

Targeted therapy in the form of selective breakpoint cluster region-abelson (BCR/ABL) tyrosine kinase inhibitor (imatinib mesylate) has successfully been introduced in the treatment of the chronic myeloid leukemia (CML). However, acquired resistance against imatinib mesylate (IM) has been reported in nearly half of patients and has been recognized as major issue in clinical practice. Multiple resistance genes and microRNAs (miRNAs) are thought to be involved in the IM resistance process.

Association of genetic variation in IKZF1, ARID5B, CDKN2A, and CEBPE with the risk of acute lymphoblastic leukemia in Tunisian children and their contribution to racial differences in leukemia incidence.

Recent genome-wide association studies (GWAS) focusing on pediatric acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15 years old, have found evidence that single-nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2), CDKN2A (9p21.