TP53 Gene 72 Arg/Pro (rs1042522) Single Nucleotide Polymorphism Contribute to Increase the Risk of B-Chronic Lymphocytic Leukemia in the Sudanese Population

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.

Combined analysis of ZAP-70 and CD38 expression in sudanese patients with B-cell chronic lymphocytic leukemia.

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.

Clinical presentation and hematological profile among young and old chronic lymphocytic leukemia patients in Sudan.

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.