Haematology

Prognostic impact of Annexin A1 expression in acute myeloid leukemia Mohmoud Gaber, Ali M Kasem, Mohamed Azzazi, Mohamed Tarif, Emad A Yusuf The Egyptian Journal of Haematology 2020 45(2):57-67 Objective The aim was to assess expression of Annexin A1 (ANXA1) on malignant myeloid blast cells and its correlation with clinical outcome, overall survival (OS), and other prognostic factors among adult Egyptian patients with acute myeloid leukemia (AML). Patients and methods A total of 60 patients with de novo AML were treated and followed up in Ain Shams University Hospitals, Hematology Unit and compared with 20 age-matched and sex-matched normal healthy controls. Expression of ANXA1 was detected by flow cytometry in bone marrow samples. Results Patients with AML had significant higher mean ANXA1 expression than mean ANXA1 expression in control at D0. The mean ANXA1 level in the favorable cytogenetics group was significantly higher than the mean ANXA1 level in the unfavorable cytogenetics group. ANXA1 was positive in 76.7% patients with AML and negative in 23.3% patients with AML. There was a significant difference between ANXA1-positive group and ANXA1-negative group of patients with AML regarding different outcomes. In ANXA1-positive group, 52.2% of patients with AML achieved complete remission (CR), whereas in ANXA1-negative group, 14.3% of patients with AML achieved CR. Highest mean ANXA1 expression was in the group of patients who had CR. High ANXA1 expression was associated with longer OS. Conclusion ANXA1 is significantly expressed in Egyptian patients with de novo AML, and its expression associated with favorable prognostic effect on clinical outcome and longer OS.

Assessment of serum interleukin-15 in adult acute leukemia patients (Egyptian sample) Mohamed M Moussa, Mahmoud Sheeba, Emad Abdel Mohsen, Mohamed Elshazly, Nour E Hussein The Egyptian Journal of Haematology 2020 45(2):68-76 Background Interleukin 15 (IL-15), proinflammatory cytokine, regulates immune system functions and controls hematopoietic cell differentiation. It promotes leukemia development through enhancing survival, proliferation, and differentiation of leukemic precursors. Aim The aim was to assess the expression of IL-15 level in adult Egyptian acute leukemia patients, its correlation with disease-free survival, overall survival and relapse rate, and its possible correlation with other prognostic parameters. Patients and methods Serum IL-15 was measured using ELISA in 30 newly diagnosed acute lymphoblastic leukemia (ALL) patients, 30 newly diagnosed acute myeloid leukemia (AML) patients, and 30 healthy controls recruited from Ain Shams University Hospital from 2017 to 2018. Results In ALL patients IL-15 was higher in patients compared with the control. IL-15 was higher in patients with non-high-risk cytogenetics compared with those with high-risk cytogenetics. Patients with high IL-15 who achieved first complete response (CR) were less than those with low/average IL-15. Patients with high IL-15 who achieved minimal residual disease (MRD) negativity were less than those with low/average IL-15. Patients with high IL-15 had shorter survival compared with those with low/average IL-15 level. Optimal cutoff value for IL-15 in predicting patient survival in ALL patients was 200 ng/l. In AML patients: IL-15 was higher in patients compared with the control. IL-15 was higher in patients with high-risk features compared with those without. Patients with high IL-15 achieved first CR less than those with average IL-15. Patients with high IL-15 achieved MRD negativity less than those with average IL-15. Patients with high IL-15 had shorter survival compared with those with low/average IL-15. Optimal cutoff value for IL-15 in predicting patient survival in AML patients was 190 ng/l. IL-15 has negative correlation with death date in AML patients. Conclusion IL-15 is a useful poor prognostic marker in newly diagnosed acute leukemia patients’ also it can be used as a predictor for CR, MRD, and survival.

Lymphocyte DNA damage in children with iron-deficiency anemia: a case–control study Aneseya P Varghese, Smriti Sinha, Seema P Sindgikar, Rathika D Shenoy, Vijaya Shenoy The Egyptian Journal of Haematology 2020 45(2):77-80 Context Iron-deficiency anemia (IDA) is a widespread yet one of the most neglected micronutrient deficiency disorder worldwide. Aims The objective was to evaluate lymphocyte DNA damage in children with anemia. Materials and methods This was a prospective case–control study. A total of 80 infants and children aged six months to twelve years were included. Fifty had IDA, whereas 30 were controls. DNA damage scoring using alkaline comet assay was done in all children. Percentage and mean and/or SEM were calculated. Comparison between cases and controls was done using Student’s t test. Analysis of variance test was used to compare the groups within the cases and controls. Pearson correlation coefficient was performed to relate the hemoglobin levels with the DNA damage. Statistical software was used for analysis. Results DNA damage scoring was significant in all the parameters in the iron-deficiency group with respect to the tail length and percentages of DNA in tail and olive moment, with a P value of 0.006, 0.002, and 0.038, respectively. A statistically significant negative correlation was found between hemoglobin levels and percentage of DNA in tail (r=−0.280; P=0.012) as well as olive moment (r=−0.240; P=0.032) Conclusion IDA was associated significantly with lymphocyte DNA damage. A significant negative correlation between hemoglobin levels and percentage of DNA and olive moment was also elucidated. The authors conclude that early intervention is needed in even mild cases of IDA.

Prognostic value of platelet glycoprotein Ibα (Kozak) gene polymorphism in patients with coronary heart disease Mohamed Sabry El-Ghonemy, Solafa El Sharawy, Mahmoud M AbdoYouseif, Shaimaa El-Ashwah, Menna T-Allah Fayez, Ahmed EL-Sebaie The Egyptian Journal of Haematology 2020 45(2):81-86 Background Coronary heart disease (CHD) is one of the leading causes of death worldwide for both men and women. It is caused by the disproportion between myocardial oxygen demand and its supply. Platelets play an important role in thrombosis and hemostasis by forming a plug at the exposed subendothelium preventing blood loss; if this process is uncontrolled it results in thrombotic events causing life-threatening disease such as myocardial infarction (MI) or ischemic stroke. Glycoprotein (GP) Ib-IX-V is a platelet membrane receptor complex containing four polypeptides, GPIbα, GPIbB, GPIX, and GPV, which plays a key role in mediating platelet activity and thrombosis. This study aimed to evaluate the role of platelet GPIbα (Kozak) gene polymorphism as a risk factor of CHD. Patients and methods This study was conducted on 120 newly diagnosed patients of CHD admitted to the Internal Medicine Hospital [46 patients with unstable angina (UA) and 74 patients with MI]. Thirty apparently healthy individuals served as a control group. The EDTA blood samples collected from patients and the control group were subjected to DNA extraction, followed by PCR amplification for the Kozak gene. Results This study showed that by taking rs2243093 TT as the reference genotype and T as the reference allele. TC, CC, TC+CC genotypes, and C allele showed a lower frequency in cases when compared with the control group, with protective effect against CHD susceptibility (P<0.05). On the other hand, no association was found in GP1bα genotypes and alleles between UA and MI subgroups (P>0.05). Conclusion Individuals carrying the C allele of (rs2243093) had protective effect against CHD including UA, MI. The rs2243093 had no association with the risk of MI in those having UA. Wild genotype (TT) was associated with higher creatine kinase-MB, while genotypes containing the risk allele (C) had lower creatine kinase-MB in CHD patients.

Sociodemographic and clinical determinants of folate deficiency among sickle cell anemia patients in Kano, North Western Nigeria Ibrahim Abdulqadir, Aisha A Galadanci, Mujtaba I Mashi, Sagir A Gumel, Aisha K Gwarzo The Egyptian Journal of Haematology 2020 45(2):87-91 Context Folate deficiency is common among sickle cell anemia (SCA) patients and could be influenced by factors such as clinical and social conditions. Sociodemographic and clinical determinants of folate deficiency have not been previously investigated among SCA patients in this environment. Aims The aim was to determine the sociodemographic and clinical factors associated with folate deficiency in SCA patients accessing care at Aminu Kano Teaching Hospital, Kano. Settings and design This was a cross-sectional study involving 110 SCA participants at steady state. Patients and methods Sociodemographic and clinical data of the participants were collated, while their folate status was determined using Roche Elecsys 2010. Statistical analysis Data were analyzed with SPSS version 21.0 and level of significance was set at P less than or equal to 0.05. Results The mean age of the participants was 14.9±7.1 years and the majority of them were men (58, 52.7%), students (96, 87.3%), and jaundiced (66, 60.0%). Age, sex, occupation of the participants, and mother’s level of education were significantly associated with folate deficiency (P<0.05). Female gender [odds ratio (95% confidence interval) for red blood cells 2.6 (1.2–5.7) and serum 2.8 (1.3–6.1)] and mothers with less than secondary education [odds ratio (95% confidence interval) for red blood cells 5.3 (1.0–27.6) and serum 4.2 (1.0–18.1)] were independent predictors of folate deficiency. Conclusion Sociodemographic and clinical characteristics are important determinants of folate deficiency in SCA. We therefore recommend periodic assessment of folate status as part of the standard care to SCA patients to prevent complications of folate deficiency.

A potential immunological diagnostic marker for acute myeloid leukemia: the expression of the immune checkpoint B and T lymphocyte attenuator Sara M Radwan, Nooran S Elleboudy, Nermeen A Nabih, Amal A El-kholy, Amany M Kamal The Egyptian Journal of Haematology 2020 45(2):92-96 Introduction Provided the physiologic tumor suppressive role a healthy immune system has, diagnosis of cancer is sometimes also regarded as a diagnosis of an immune dysfunction. Immunoediting refers to the change of immune system response from tumor protection to tumor promotion, favoring the growth of poorly immunogenic clones that have the ability to evade the immune response. Among the mechanisms by which the tumor cells bypass the immune system is immune checkpoints. Which are immune inhibitory pathways responsible for self-tolerance and limiting self-tissue damage by controlling the magnitude and duration of the immune reaction. Objective Studying the expression of the novel immune checkpoint BTLA in patients with AML and evaluate its clinicopathological and diagnostic significance. Patients and methods We investigated the expression of BTLA gene in 60 AML cases and 15 healthy controls using RT-PCR. Results The current study revealed that significant up regulation of BTLA mRNA expression in AML patients as in comparison with the control group (P=0.024). Discussion These results provide a basis for the perception that BTLA upregulation is involved in inhibition of antitumor immunity and that high BTLA expression level can be made use of as a diagnostic marker in patients with AML.

Longitudinal assessment of the impact of tuberculosis infection and treatment on monocyte–lymphocyte ratio, neutrophil–lymphocyte ratio, and other white blood cell parameters Chizoba O Okeke, Grace I Amilo, Martin O Ifeanyichukwu, Ejeatuluchukwu O Obi The Egyptian Journal of Haematology 2020 45(2):97-104 Context Tuberculosis (TB) is a major infectious disease usually marked by alterations in white blood cell (WBC) parameters which are known to play a major role in the normal body response to infections. Aim The aim was to assess the impact of TB infection and treatment on monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and other WBC parameters in TB individuals before and in the course of therapy. Settings and design This was a longitudinal follow-up study that included 60 TB-infected individuals, age 18 and 80 years. The TB individuals were recruited at Mile-Four Hospital Abakaliki before initiation of therapy and followed up at 2 months and 6 months into treatment. Materials and methods TB diagnosis was done using both Ziehl–Neelsen acid fast bacilli test and GeneXpert Mycobacterium tuberculosis/rifampicin assay. Whole blood collected in dipotassium ethylenediamine tetraacetic acid was used for the measurement of total white blood cell count and differential white cell count (neutrophil, lymphocyte, monocyte, eosinophil) and packed cell volume. The MLR and NLR were calculated. Statistical Package for the Social Sciences (SPSS), version 22 was used for statistical analysis. Results The findings showed that total white cell count, neutrophil count, lymphocyte count, eosinophil count, and monocyte count (×109/l) were all significantly decreased after 2-month treatment compared with the pretreatment values (P<0.05) and all except monocyte was significantly increased after 6-month treatment (P<0.05). There was a significant decrease in NLR and MLR after 2 months of treatment that was maintained after 6 months of treatment. Moreover, the packed cell volume (l/l) increased significantly after 2 months of treatment and decreased significantly after 6 months of treatment. Conclusion TB is associated with significant changes in NLR, MLR, and other WBC parameters which might be possible markers to explore as a prognostic index in TB disease.

β-catenin mutations in acute myeloid leukemia Buket A Gunes, Tulin Ozkan, Aynur K Gurel, Yalda Hekmatshoar, Meral Beksac, Asuman Sunguroglu The Egyptian Journal of Haematology 2020 45(2):105-110 Background Acute myeloid leukemia (AML) is a hematopoietic stem cell disorder characterized by uncontrolled proliferation and impaired differentiation of normal hematopoietic stem or progenitor cells. Various pathways like RAF/MEK/ERK, PI3K/AKT, receptor tyrosine kinases, members of RAS family, and Wnt/β-catenin are disrupted in AML. Stabilization of β-catenin, the key point of activated Wnt/β-catenin pathway, has been shown in AML in various studies. One of the mechanisms that may lead to the β-catenin stabilization is the mutations in exon 3 at its N-terminal domain, where β-catenin is phosphorylated particularly during the degradation process, and these mutations have been investigated in chronic myeloid leukemia and many other cancer types. Aim β-Catenin gene exon 3 mutations were analyzed in this study with the aim of determining the relationship between mutations and molecular biology of AML. Patients and methods In this study, we examined β-catenin gene mutations in AML cell line U937 and 31 untreated patients with AML by using the DNA sequence analysis for the first time in a Turkish population. Results No β-catenin gene exon 3 mutations were detected in patients with AML and the cell line. Conclusion β-catenin mutations have been detected in various types of cancer; however, the authors did not find any mutation in this gene, which may be responsible for the activation of Wnt signaling in AML. Further research is required to understand the mechanisms apart from mutations that may induce β-catenin stabilization in AML.

Hyperhomocysteinemia is associated with deep vein thrombosis in Nigerian patients Sunday P Ogundeji, Taiwo R Kotila, Foluke A Fasola The Egyptian Journal of Haematology 2020 45(2):111-114 Background Hyperhomocysteinemia is a modifiable risk factor associated with deep venous thrombosis (DVT). Low serum concentrations of vitamin B12 and folate are modifiable causes of hyperhomocysteinemia. This study was carried out to determine the prevalence of hyperhomocysteinemia in Nigerian patients with DVT and also to assess the association of homocysteine with vitamin B12 and folate. Patients and methods A case–control study was carried out in which serum homocysteine, vitamin B12, and folate levels were measured in 45 Doppler ultrasound confirmed cases of DVT and 43 controls. Hyperhomocysteinemia was defined by serum levels more than 15.0 μmol/l, low serum folate less than 3 μg/l, and low serum vitamin B12 less than 160 ng/l. Results The prevalence of hyperhomocysteinemia in DVT patients was 20 (44.4%) compared with four (9.35%) in the control (P<0.001). The mean serum folate and vitamin B12 levels of DVT patients were 8.7±4.8 and 725±475, while that of the controls were 9.3±3.8 μg/l and 821±393 ng/l (P=0.51 and 0.36), respectively. There was no correlation between hyperhomocysteinemia and low vitamin B12 and folate levels. Conclusion Hyperhomocysteinemia may be a risk factor for DVT in the Nigerian population but may not be responsible for thrombosis in all cases. There was however no significant correlation between serum level of homocysteine and serum levels of vitamin B12 and folate in DVT patients. Therefore, larger sized sample studies should be carried out to investigate the relationship between hyperhomocysteinemia and related vitamins as well as genetic causes of hyperhomocysteinemia in DVT patients in our environment.

Burkitt lymphoma presenting with nasopharyngeal mass and generalized lymphadenopathy in a HIV-positive patient Manasi Mundada, Faiq Ahmed, Rachna Khera, Sudha Murthy, Pavan Kumar Boyella The Egyptian Journal of Haematology 2020 45(2):115-117 Burkitt lymphoma is an aggressive B-cell neoplasm arising from the germinal center B cells. Clinically, it exists in three forms: endemic, sporadic, and immunodeficiency associated. Immunodeficiency-associated Burkitt lymphoma is usually extranodal and occurs with a CD4 count more than 200 μl. We report a retrospective study of a 47-year-old male patient, seropositive for HIV infection, presenting with nasopharyngeal mass and generalized lymphadenopathy. His CD4 count was 192 cells/μl, and lactate dehydrogenase was high. Diagnosis was established by biopsy, immunohistochemistry, and fluorescence in-situ hybridization. He was treated with chemotherapy. The disease progressed to involve central nervous system despite treatment. He received palliative radiotherapy and was stable at 11-month follow-up. This report highlights the uncommon clinical presentation, heavy disease burden, and progression of the disease in a HIV seropositive patient.

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