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Background: The P-glycoprotein (P-gp) is one of the mechanisms of Imatinib (IM) resistance in chronic myeloid leukemia (CML). P-gp has been identified as an efflux pump involved in releasing of IM outside CML cells. To date, the P-gp involvement in the IM resistance development was not completely understood. Therefore, the present study aimed at measuring the P-gp expression level on lymphocytes from Tunisian patients with CML and correlating this level with a molecular response to IM., Method: The expression of P-gp on peripheral blood lymphocytes from 59 Tunisian patients with CML (27 IM responder patients vs 32 IM non-responder patients) was evaluated by flow cytometry., Result: Our finding showed significantly positive expression of P-gp in the lymphocytes from the IM non-responder group when compared to the IM-responder group (P = .001). In IM non-responder CML patients, the comparison between CCyR achievers and non-achievers showed a high mean fluorescence intensity (MFI) of P-gp expression in patients who did not achieve their CCyR (P = .001). The comparison between patients with primary and secondary resistance to IM showed an increasing MFI value in patients with primary resistance to IM (P = .001). Besides, the comparison between nilotinib-treated and dasatinib-treated patients proved a high value of MFI in nilotinib-treated patients (P = .001)., Conclusion: The overexpression of P-gp on lymphocytes has significantly correlated with the failed molecular response to IM in patients with CML., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: This work aimed to evaluate oxidative stress in chronic myeloid leukemia (CML) patients treated with tunisian (IM) vs controls and in CML patients with resistance to IM vs patients without resistance to IM., Methods: The study included 40 CML patients and 34 controls. Of 40 patients with CML, 26 patients were developed in resistance to IM. The oxidant/antioxidant markers were evaluated by spectrophotometric methods for all used samples., Results: For CML patients, increased malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels were found compared to controls (P < .001; P = .01). Higher catalase (CAT) activity (P = .048) and lower superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, reduced Glutathione (GSH) and vitamin C levels were found in CML patients (P < .001). The comparison between the resistant vs no-resistant CML patients revealed higher MDA level (P = .02) and CAT and SOD activities in IM-resistant patients (P = .04, P = .03). GPx activity was reduced (P = .04). Furthermore, increased mean ratio of MDA/GSH, MDA/GPx, and SOD/(GPx + CAT) was found in IM-resistant patients as compared with no-resistant (P = .01, P = .01, P = .035). The mean ratio of GPx/GSH in the IM-resistant CML patients was lower than in IM no-resistant one (P = .039). For IM-resistant patients, we found negative correlation between MDA level and the ratio SOD/(CAT + GPx) (r = -0.46, P = .002); and positive correlation between SOD and (CAT + GPx) activities (r = 0.38, P = .06) and between GSH level and GPx activity (r = 0.53, P = .01)., Conclusions: Our results have shown a highly disturbed oxidative profile in IM-resistant CML patients as compared to no-resistant. The H 2 O 2 has a key role in the resistance to IM treatment., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Inherited factor XIII (FXIII) deficiency is a rare bleeding disorder characterized by an umbilical bleeding during the neonatal period, delayed soft tissue bruising, mucosal bleeding spontaneous intracranial hemorrhage, and soft tissue hemorrhages. Congenital FXIII deficiency is an autosomal recessive disorder, usually attributed to a defect in the FXIIIA and B subunits coding, respectively, by F13A and F13B genes. The aim of this study was to determine the molecular defects responsible for congenital factor XIII deficiency in eight Tunisian families. Molecular analysis was performed by direct DNA sequencing of polymerase chain reaction amplified fragments spanning the coding regions and splice junctions of the FXIIIA subunit gene (F13A) in probands and in families' members and compared with the reported sequence of this gene. In all patients, FXIIIA activity was undetectable and the FXIIIB was within the normal range. Direct sequencing of the F13A gene in all probands showed two mutations: the c.869insC mutation found in eight patients and the c.1226G > A transition found in only one. We also confirmed the presence of a founder effect for the first frequent mutation by using two microsatellite markers, HUMF13A01 and a generated ployAC marker (HUMF13A02). We describe here molecular abnormalities found in nine Tunisian probands diagnosed with FXIIIA deficiency. The identification of the founder mutation and polymorphisms allowed a genetic counseling in relatives of these families, and the antenatal diagnosis is now available.