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Ezeldine K Abdalhabib,1 Badr Alzahrani,1 Muhammad Saboor,2– 4 Alneil Hamza,1 Elyasa M Elfaki,1 Fehaid Alanazi,1 Fawaz O Alenazy,1 Abdulrahman Algarni,5 Ibrahim Khider Ibrahim,6 Hozifa A Mohamed,7 Ayman Hussein Alfeel,8 Nahla Ali Alshaikh3,4 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia; 2Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; 3Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 4Medical Research Center (MRC), Jazan University, Jazan, Saudi Arabia; 5Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia; 6Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 7Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 8Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Ayman Hussein Alfeel, Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates, Email aymanalfeel@gmail.com Muhammad Saboor, Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates, Tel +971 56 443 2008, Email msaboor@jazanu.edu.saPurpose: Single-nucleotide polymorphism (SNP) in the promoter region of the IL-10 gene can increase susceptibility to tumor development. The current study aimed to explore the genotypic frequency of interleukin-10 (IL-10) rs1800896 polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and validate whether this SNP is a risk factor for adult ALL.Patients and Methods: This case–control study was based on a subset of newly diagnosed 154 adult patients with ALL recruited from the Radiation and Isotope Center in Khartoum (RICK) and 154 healthy controls from the same geographical area. Genomic DNA was used for the genotyping of rs1800896 polymorphism through allele-specific polymerase chain reaction (PCR) assays.Results: The genotypic frequencies of rs1800896 showed a statistically significant association of AG and AA genotypes with adult ALL (p< 0.001). Combined genotypes AG+GG vs AA also showed a positive association of rs1800896 with adult ALL (OR=4.89). The allelic frequencies of G and A did not show any significant difference in adult patients with ALL compared with the control group. AG rs1800896 genotype showed an increased risk of B and T ALL (OR=2.51 and 4.70, respectively). Age at diagnosis, gender, and immunophenotype (B vs T ALL) did not exhibit any association of rs1800896 with ALL in this patient group.Conclusion: rs1800896 polymorphism is associated with an increased risk of ALL in adult patients irrespective of the age at diagnosis, gender, and immunophenotype of ALL.Keywords: acute lymphoblastic leukemia, polymorphism, IL-10, – 1082 (A>G), rs1800896

Deep vein thrombosis (DVT) is a critical condition and a potential cause of mortality and morbidity in Africa and worldwide with a high recurrence rate. The study was designed to assess the roles of natural anticoagulants and fibrinolytic regulatory factors in the development of DVT in Sudanese patients. A case-control study was conducted in Omdurman Teaching Hospital, Khartoum State over a period of 1 year. The study enrolled 200 patients diagnosed with DVT and 200 age-matched and gender-matched controls. Demographic data and data on acquired risk factors were collected using a semi-structured questionnaire. Protein C (PC), protein S (PS), antithrombin III (AT-III), thrombin-activable fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor-1 (PAI-1) were measured in patients and controls. Among the patients with DVT, 5.5% had PC deficiency, 8.5% had PS deficiency, and 3% had AT-III deficiency. Elevated TAFI and PAI-1 levels were demonstrated in 1.5 and 0.5% of patients, respectively. Risk factors for DVT (overweight, surgical history, and family history of DVT) were remarkably higher in patients than in controls. Among the female participants, pregnancy and usage of oral contraceptive pills were the highest associated risk factors for DVT. The findings concluded that the early assessment of risk factors, including the measurements of natural inhibitors, can predict the occurrence of DVT before it is actually detected in patients.

Ezeldine K Abdalhabib,1 Badr Alzahrani,1 Fehaid Alanazi,1 Abdulrahman Algarni,2 Ibrahim Khider Ibrahim,3 Hozifa A Mohamed,4,5 Hassan A Hamali,6 Abdullah A Mobarki,6 Gasim Dobie,6 Muhammad Saboor6,7 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia; 2Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Borders University, Arar, Saudi Arabia; 3Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 4Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 5Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Sudan International University, Khartoum, Sudan; 6Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 7Medical Research Center (MRC), Jazan University, Jazan, Saudi ArabiaCorrespondence: Muhammad Saboor, Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan, Saudi Arabia, Tel +966 54 495 9029, Email msaboor@jazanu.edu.saPurpose: Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL.Patients and Methods: This case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control.Results: The genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = < 0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42– 29.74, P < 0.001).Conclusion: Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.Keywords: GSTT1, GSTM1, polymorphism, acute lymphoblastic leukemia

This work intended to formulate bio-nanocomposites of zinc oxide (ZnO), titanium oxide (TiO2), chitosan, and escin, characterize their physical properties, and evaluate their antimicrobial and anticancer properties. X-ray diffractometers (XRD) and scanning and transmission electron microscopes were applied to characterize the morphology and ultrastructure of chemically synthesized bio-nanocomposites. To investigate the functional groups of bio-nanocomposites, we used Perkin–Elmer spectrometers for Fourier transform infrared (FTIR) analysis and photoluminescence (PL) spectroscopy for PL spectrum analysis. Antimicrobial activities against bacterial and fungal strains were tested with agar well diffusion. Bio-nanocomposites were tested for anticancer effects on a MOLT4 blood cancer cell line using morphological analysis, methyl thiazole tetrazolium assay, apoptosis by acridine orange/ethidium bromide, and mitochondrial membrane potential (ΔΨm). In XRD, FTIR, and PL, the active compounds of ZnO–TiO2, chitosan, and escin peaks were observed. Our bio-nanocomposites demonstrated antimicrobial activity against bacterial and fungal pathogens. The bio-nanocomposite was cytotoxic to MOLT4 cells at an IC50 concentration of 33.4 µg·mL−1. Bio-nanocomposites caused cytotoxicity, changes in cell morphology, and mitochondrial membrane potential degradation, all of which resulted in apoptotic cell death. MOLT4 cells were found to be responsive to bio-nanocomposites based on ZnO–TiO2–chitosan–escin.

Ezeldine K Abdalhabib,1 Denise E Jackson,2 Badr Alzahrani,1 Elyasa Elfaki,1 Alneil Hamza,1 Abdelbaset Mohamed Elasbali,1 Fehaid Alanazi,1 Abdulrahman Algarni,3 Ibrahim Khider Ibrahim,4 Muhammad Saboor5,6 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, AlQurayyat, Jouf University, Sakaka, Saudi Arabia; 2Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, RMIT University, Victoria, Australia; 3Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Borders University, Arar, Saudi Arabia; 4Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 5Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 6Medical Research Center (MRC), Jazan University, Jazan, Saudi ArabiaCorrespondence: Muhammad SaboorDepartment of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan, Saudi ArabiaTel +966 54 495 9029Email msaboor@jazanu.edu.saEzeldine K AbdalhabibDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences-AlQurayyat, Jouf University, Saudi ArabiaTel +966 538949566Email ezeldine@ju.edu.saPurpose: DNA damage to hematopoietic progenitor cells is an essential factor for leukemia development as a failure of the host DNA repair system to fix errors in DNA. This study aimed to assess the association of XRCC1 gene polymorphisms including Arg194Trp, Arg399Gln, and Arg280His with the risk of development of CML in Sudanese population.Patients and Methods: The present study was conducted on 186 newly diagnosed patients with CML, aged 19– 70 years (118 males and 68 females; mean age of 46.15± 13.91 years) and 186 normal healthy controls (123 males and 63 females; mean age of 44.94± 8.97 years). Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the XRCC1 (Arg194Trp, Arg399Gln, and Arg280His) gene polymorphisms.Results: The genotypic frequencies of Arg399Gln polymorphism in cases were 131 (70.4%) homozygous Arg/Arg, 46 (24.7%) homozygous Gln/Gln, and 9 (4.8%) heterozygous Arg/Gln as compared to the controls ie, 153 (82.3%), 73 (14.5%), and 6 (3.2%), respectively. The Arg399Gln variant genotypic frequencies significantly differed between the cases and controls (χ2 = 7.249, P = 0.027). By comparison, no statistically significant difference was observed in the variant genotype frequencies between the cases and controls in terms of Arg194Trp and Arg280His polymorphisms.Conclusion: XRCC1 Arg399Gln gene polymorphism might have an important role in increasing the risk of chronic myeloid leukemia among Sudanese patients. Furthermore, all tested three polymorphisms showed no association of risk of the development of CML with age and gender.Keywords: XCCR1, chronic myeloid leukemia, polymorphism

The Ig-ITIM bearing receptors, PECAM-1 and CEACAM1, have been shown net negative regulators of platelet–collagen interactions and hemiITAM signaling pathways. In this study, a double knockout (DKO) mouse was developed with deleted PECAM-1 and CEACAM1 to study their combined contribution in platelet activation by glycoprotein VI, C-type lectin-like receptor 2, protease activated receptor (PAR4), ADP purinergic receptors, and thromboxane receptor (TP) A2 pathways. In addition, their collective contribution was examined in thrombus formation under high shear and microvascular thrombosis using in vivo models. DKO platelets responded normally to ADP purinergic receptors and the TP A2 pathway. However, DKO platelets released significantly higher amounts of P-selectin compared with hyper-responsive Pecam-1−/− or Ceacam1−/− versus wild-type (WT) upon stimulation with collagen-related peptide or rhodocytin. In contrast, DKO platelets showed increased amounts of P-selectin exposure upon stimulation with PAR4 agonist peptide or thrombin but not Pecam-1−/− , Ceacam1−/− , or WT platelets. Blockade of phospholipase C (PLC) or Rho A kinase revealed that DKO platelets enhanced α-granule release via PAR4/Gαq/PLC signaling without crosstalk with Src/Syk or G12/13 signaling pathways. Severely delayed clot retraction in vitro was observed in DKO phenotype. The DKO model revealed a significant increase in thrombus formation compared with the hyper-responsive Ceacam1−/− or Pecam-1−/− versus WT phenotype. DKO platelets have similar glycoprotein surface expression compared with Pecam-1−/− , Ceacam1−/− , and WT platelets. This study demonstrates that PECAM-1 and CEACAM1 work in concert to negatively regulate hemiITAM signaling, platelet–collagen interactions, and PAR4 Gαq protein- coupled signaling pathways. Both PECAM-1 and CEACAM1 are required for negative regulation of platelet activation and microvascular thrombosis in vivo.

TNF–α influences lymphomagenesis by upregulating proinflammatory and antiapoptotic pathways. In this study, we evaluated the frequency of TNF–α rs1800629 (–308 G>A) polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and its correlation with age at diagnosis, gender and subtype of ALL. In this case control study, a total of 330 individuals were recruited, including 165 newly diagnosed adult patients with ALL, from the Radiation and Isotope Center in Khartoum (RICK) and 165 healthy normal controls. TNF–α rs1800629 polymorphism was tested through allele-specific polymerase chain reaction (PCR) assay. The frequency of the rs1800629 GA genotype was high (70.9% vs. 60%, OR = 1.84) in the patient group as compared to healthy controls, whereas GG and AA genotypes did not exhibit any statistically significant difference between controls and patients. Based on subtype, GG and GA rs1800629 genotypes showed increased risk of B-ALL (OR 0.46 and 2.12, respectively), whereas rs1800629 GG, GA and AA genotypes did not show any disease association with T-ALL (p > 0.05). Age at diagnosis and gender did not exhibit any association of rs1800629 with ALL in the patient group. In conclusion, rs1800629 is associated with high risk of adult B-ALL, with an insignificant effect of age at diagnosis and gender.

Multiple myeloma (MM), a plasma cell malignancy, is characterised by lesions in multiple bones involving transformed, matured post-follicular B cells. The course of the disease involves an initial development of monoclonal gammopathy of undetermined significance (MGUS), followed by smouldering MM, before the full MM disease emerges. Despite novel therapies, MM remains incurable, managed by combination therapies, including proteasome inhibitors (PIs), immunomodulators (IMiDs) and anti-human CD38 (daratumumab). MM patients have an increased risk of thromboembolic events due to combination treatments with IMiDs, PIs and anti-human CD38 antibody, and steroids. This review will examine the efficacy and pro-thrombotic effects of MM therapies.

Ezeldine K Abdalhabib,1 Denise E Jackson,2 Badr Alzahrani,1 Elyasa M Elfaki,1 Alneil Hamza,1 Fehaid Alanazi,1 Elryah I Ali,3 Abdulrahman Algarni,3 Ibrahim Khider Ibrahim,4 Muhammad Saboor5,6 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences-Al Qurayyat, Jouf University, Sakaka, Saudi Arabia; 2Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, RMIT University, Victoria, Australia; 3Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia; 4Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 5Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 6Medical Research Center (MRC), Jazan University, Jazan, Saudi ArabiaCorrespondence: Muhammad SaboorDepartment of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan, Saudi ArabiaTel +966 54 495 9029Email msaboor@jazanu.edu.saPurpose: Glutathione S-transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML.Patients and Methods: This case–control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers.Results: GSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys.Conclusion: In conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.Keywords: GSTT1 null polymorphism, GSTM1, XPD, chronic myeloid leukemia

Purpose DNA damage to hematopoietic progenitor cells is an essential factor for leukemia development as a failure of the host DNA repair system to fix errors in DNA. This study aimed to assess the association of XRCC1 gene polymorphisms including Arg194Trp, Arg399Gln, and Arg280His with the risk of development of CML in Sudanese population. Patients and Methods The present study was conducted on 186 newly diagnosed patients with CML, aged 19–70 years (118 males and 68 females; mean age of 46.15±13.91 years) and 186 normal healthy controls (123 males and 63 females; mean age of 44.94±8.97 years). Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the XRCC1 (Arg194Trp, Arg399Gln, and Arg280His) gene polymorphisms. Results The genotypic frequencies of Arg399Gln polymorphism in cases were 131 (70.4%) homozygous Arg/Arg, 46 (24.7%) homozygous Gln/Gln, and 9 (4.8%) heterozygous Arg/Gln as compared to the controls ie, 153 (82.3%), 73 (14.5%), and 6 (3.2%), respectively. The Arg399Gln variant genotypic frequencies significantly differed between the cases and controls (χ2 = 7.249, P = 0.027). By comparison, no statistically significant difference was observed in the variant genotype frequencies between the cases and controls in terms of Arg194Trp and Arg280His polymorphisms. Conclusion XRCC1 Arg399Gln gene polymorphism might have an important role in increasing the risk of chronic myeloid leukemia among Sudanese patients. Furthermore, all tested three polymorphisms showed no association of risk of the development of CML with age and gender.