RESUMEN
BACKGROUND: several studies have been performed to investigate the association of TNF-α-308G>ASNP and CLL susceptibility However, the results are inconsistent. This study aimed to investigate the association between TNF-α-308G>ASNP of the TNF-α gene and CLL risk in the Sudanese population and correlated genotypes with clinicopathological features. METHODS: A case-control study was conducted in Khartoum state, during the period from April 2017 to April 2018, involved 110 CLL patients and 50 healthy volunteers. Physical examination, Complete Blood Count, and immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as Rai and Binet were studied. CD38 and ZAP70 were performed by Flow Cytometry. Blood samples were collected from all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit and analyzed TNF-α-308G>ASNP by using AS-PCR. The statistical analysis was performed using SPSS. RESULTS: TNF-α-308G>A genotype frequencies were GG (10.0%), GA (87.3%), and AA (2.7%) among the CLL patients, and GG (14.0%), GA (80.0%), and AA (6.0%) in the control group. The comparison of CLL patients with the control group did not show any statistically significant relationship for the genotypic and allelic frequencies. Furthermore, no association was observed between the TNF-α-308G>ASNP and gender, hematological parameters, clinical stages systems, CD38 expression, and ZAP-70 expression. The presence of theTNF-α-308Aallele was associated with a lower mean age. CONCLUSIONS: These results indicate that TNF-α-308G>A genotypes are not involved in the predisposition to the development of CLL. TNF-α-308A allele carrier induced to development of CLL at an earlier age.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , Factor de Necrosis Tumoral alfa , Humanos , Alelos , Factor de Necrosis Tumoral alfa/genética , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , GenotipoRESUMEN
OBJECTIVE: The present study was conducted to examine the association between the IL-10-1082A>G (rs 1800896) polymorphism and risk of Chronic Lymphocytic Leukemia and to assess the correlation between this polymorphism and clinicopathological characters. METHODS: A case-control study was conducted in Khartoum state, Sudan, during the period from April 2017 to April 2018, involved 110 CLL patients and 80 healthy volunteers as a control group. Physical examination, complete blood count, and immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as Rai and Binet were studied. CD38 and ZAP70 were performed by flow cytometry. Blood samples were collected from all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit and analyzed IL-10-1082A>G polymorphism by using Allele Specific-Polymerase Chain Reaction. The statistical analysis was performed using statistical package for social sciences version 23.0 software. RESULTS: Frequency of AA, AG, and GG genotypes was 32.7%, 55.5%, and 11.8% for the patient group and 31.25%, 51.25%, and 17.5% in the control group, respectively. The genotype of IL-10 (-1082A>G) did not associate with susceptibility of CLL in our population. The study showed that the G allele of the IL-10 gene (-1082A>G) is associated with the male sex. However, no significant association was found between -1082A>G genotype and clinicopathological characters. CONCLUSION: Our results do not support the involvement of the IL-10 -1082A>G promoter gene polymorphism in the increased CLL susceptibility. IL-10-1082G allele (IL-10-1082AG or IL-10-1082GG) was found more frequently in males. Furthermore, no association was observed between the IL-10-1082A>G polymorphism and clinical stages systems as well as established poor prognostic markers. Finally, within the group of patients with CLL, there was no difference in the age at diagnosis and hematological parameters according to genotype distributions.
Asunto(s)
Interleucina-10 , Leucemia Linfocítica Crónica de Células B , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interleucina-10/genética , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/genética , Masculino , Factores de RiesgoRESUMEN
Objective: This study aimed at exploring the association of TP53 72Arg/Pro polymorphism and Risk of Chronic Lymphocytic Leukemia and to assess the correlation between TP53 72Arg/Pro polymorphism and clinical parameter, hematological profile and some biological prognostic markers among Sudanese patients with chronic lymphocytic leukemia. Methods: A case-control study was conducted in Khartoum state, Sudan, during the period from April 2017 to April 2018, involved 110 B-CLL patients and 80 healthy volunteers as a control group. Physical examination, Complete Blood Count and Immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as Rai and Binet were studied. CD38 and ZAP70 were performed by Flow Cytometry. Blood samples were collected from all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit (Germany) and analyzed TP53 codon 72Arg/Pro Polymorphism by using AS-PCR. The statistical analysis was performed using SPSS version 23.0 software (Chicago, IL, USA). Results: the Arg/Pro was the most frequent genotype in B-CLL patients(50%), followed by Arg/Arg (25.5%) and Pro/Pro (24.5%), whereas in healthy control group Arg/Pro was the most frequent (47.5%), followed by Arg/Arg (45%) and Pro/Pro (7.5%). Our data indicate a higher frequency of homozygous Pro/ Pro in the B-CLL patients as compared to controls with an OR of 4.01 for the Pro/Pro genotype and lower frequency of Arg/Arg genotype in CLL patients as compared to controls with an OR of .42 for the Arg/Arg genotype. Also, the Pro allele showed higher risk than Arg allele (P value=0.000, OR 2.23, 95% CI=1.45-3.41). No significant association between gender, clinical staging systems (Rai, Binet), biological prognostic markers (CD38 expression or ZAP70 expression), and TP53 codon 72Arg/Pro polymorphisms, except Arg/Arg genotype tended to be associated with younger age (P =0.04). Conclusion: Our data suggested that Pro/Pro genotype contribute to increased susceptibility to B-Chronic Lymphocytic Leukemia risk in our population tenfold higher than those had Arg/Arg genotype.
Asunto(s)
Dipéptidos/genética , Predisposición Genética a la Enfermedad/genética , Leucemia Linfocítica Crónica de Células B/genética , Polimorfismo de Nucleótido Simple/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Codón , Femenino , Genotipo , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Sudán , Adulto JovenRESUMEN
OBJECTIVE: To investigate the ZAP-70 and CD38 expressions and their combined expressions in Sudanese B-CLL patients and their relationships with clinical and hematological characteristics as well as the disease staging at presentation. RESULTS: In the present cross-sectional descriptive study, analysis of ZAP-70 expression showed that 36/110 (32.7%) patients positively expressed ZAP-70 and insignificant higher presentation in intermediate and at advanced stages as well as no correlation was seen with hematological parameters and clinical features compared with negatively ZAP-70, on the other hand, 41/110 (37.3%) were CD38+ and no significant correlation was shown with the stage at presentation, clinical characteristics (except Splenomegaly, P = 0.02) and hematological parameters. However, in combined expressions of both ZAP-70 and CD38 together, 20/110 (18.2%) were concordantly ZAP-70+/CD38+, 53/110 (48.2%) concordantly ZAP-70-/CD38- and 37/110 (33.6%) either ZAP-70+ or CD38+, and these three groups showed insignificant correlation with clinical (except Splenomegaly, P = 0.03) and hematological parameters, and the stage at presentation. Our data showed the combined analysis of these two markers, lead to classify our patients into three subgroups (either concordant positive, negative or discordant expressions) with statistically insignificant correlation with clinical presentation (except Splenomegaly), hematological parameters and stage at presentation of B-CLL patients.
Asunto(s)
ADP-Ribosil Ciclasa 1/genética , Biomarcadores de Tumor/genética , Leucemia Linfocítica Crónica de Células B/diagnóstico , Glicoproteínas de Membrana/genética , Esplenomegalia/diagnóstico , Proteína Tirosina Quinasa ZAP-70/genética , ADP-Ribosil Ciclasa 1/sangre , ADP-Ribosil Ciclasa 1/inmunología , Adulto , Anciano , Linfocitos B/inmunología , Linfocitos B/patología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/inmunología , Estudios Transversales , Femenino , Expresión Génica , Humanos , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Glicoproteínas de Membrana/sangre , Glicoproteínas de Membrana/inmunología , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Esplenomegalia/genética , Esplenomegalia/inmunología , Esplenomegalia/patología , Sudán , Proteína Tirosina Quinasa ZAP-70/sangre , Proteína Tirosina Quinasa ZAP-70/inmunologíaRESUMEN
OBJECTIVE: To assess the clinical presentation and hematological profile among young (≤ 55 years) and old (> 55 years) chronic lymphocytic leukemia patients in Sudan. RESULT: In the present cross-sectional descriptive study, out of 110 cases studied, among them 31 (28.2%) were young (≤ 55 years) patients with mean age 48 years, and 79 (71.8%) were elder patients (> 55 years) with mean age 66 years, the overall mean age was 62.97 ± 12.06 with range (22-85 years), and 79 (71.8%) were males and 31 (28.2%) were females (M:F = 2.6:1) (P = 0.000). (7.3%) were asymptomatic, 61 (55.5%) presented with nonspecific complains. Generalized lymphadenopathy was seen in 52 (47.27%) with elder predominance (P = 0.03). Splenomegaly, hepatomegaly, thrombocytopenia and anemia were seen in 54 (49.1%), 14 (12.7%), 43 (39.1%) and 38 (34.5%) of patients respectively with male predominance. 54 (49.1%) and 42 (38.18%) of patients presented at Rai high risk and Binet C stages respectively with nearly same age and sex distribution. CLL in Sudan is a disease of elders, same as seen in literature, with high male to female ratio. In general hematological parameters means were noted to be distributed equally according to age and sex groups. Majority of patients were presented with nonspecific symptoms and nearly half of patients presented at late stages as reported in most developing countries.
Asunto(s)
Anemia , Hepatomegalia , Leucemia Linfocítica Crónica de Células B , Linfadenopatía , Esplenomegalia , Trombocitopenia , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/epidemiología , Anemia/etiología , Femenino , Hepatomegalia/sangre , Hepatomegalia/epidemiología , Hepatomegalia/etiología , Humanos , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/epidemiología , Linfadenopatía/sangre , Linfadenopatía/epidemiología , Linfadenopatía/etiología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Esplenomegalia/sangre , Esplenomegalia/epidemiología , Esplenomegalia/etiología , Sudán/epidemiología , Trombocitopenia/sangre , Trombocitopenia/epidemiología , Trombocitopenia/etiología , Adulto JovenRESUMEN
OBJECTIVE: The objective of this study was to evaluate the cluster of differentiation-38 (CD38) expression in Sudanese patients with chronic lymphocytic leukemia (CLL) and to determine its association with clinical and laboratory characteristics of the disease. RESULTS: We conducted a cross-sectional study on 99 patients diagnosed with CLL in Khartoum Oncology Hospital in Khartoum, Sudan. Immunophenotyping and CD38 expression levels were measured with four-color flowcytometry. The results of physical examination and blood analyses were used for assigning a modified Rai clinical staging system. The collected data were analyzed using the Statistical Package for the Social Science, version 22 (SPSS Inc., Chicago, IL, USA). According to our findings, the frequencies of 7%, 20%, and 30% cutoff levels of CD38 expressions were 68.7%, 41.4%, and 36.4% respectively. CD38 cutoff level of 7% showed a significant association with hemoglobin concentration (P = 0.04), whereas other cutoff levels showed insignificant results. All the three cutoff levels showed insignificant associations with the other clinical and laboratory variables. In conclusion, the CD38 expression at a cutoff level of 7% seems to be more valuable clinically than higher cutoff levels in Sudanese CLL patients.