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Background: CBP, CEBPA and DNMT3A are tumor suppressor genes whose dysfunction has been reported in hematologic malignancies. Acute myeloid leukemia is the most common type of white cell neoplasm among adults. Our aim is to assess the expression level of CBP, CEBPA and DNMT3A genes in an Egyptian cohort with AML. We investigated the correlation between the selected genes’ mRNA levels and their association with the clinical characteristics and survival. MethodsA total of 53 adult participants diagnosed with AML were enrolled in the study. Quantitative RT-PCR was used to assess CBP, CEPBA and DNMT3A expression. Results: There was no significant difference between males and females in the relative expression level of CBP, CEBPA, and DNMT3A. Similarly, none of the three genes showed statistically significant correlation with age at the time of diagnosis or FAB subtypes of AML. The correlation matrix of the three genes detected a significant correlation only between CBP and CEBPA expression (rS= .518, P=0.000). Survival analysis of our cohort showed no association of any of the studied genes with neither overall nor disease free survival. Conclusion: Our finding may indicate a complementary role of CBP and CEBPA in AML pathogenesis; however, further investigation on larger samples is still warranted to study the relationship of these genes with AML survival.

Background: Chronic lymphatic leukemia (CLL) is the most common hematological malignancy in adults presenting with varied clinical courses. There is an increased demand for establishing known prognostic factors for stratifying CLL patients. Aim of the work: To investigate the expression of soluble form of human leucocyte antigen-G (HLA-G) & CD 38 in CLL and to correlate our findings with a variety of clinical and laboratory variables. Patients and methods: The study included thirty newly diagnosed CLL patients. They were 18 males and 12 females with age ranged from 49–65 (a mean of 57.5 years old). Diagnosis of CLL was confirmed by flow cytometric immunophenotyping using standard lymphoma panel. CD38 expression was determined by flow cytometry. S. HLAG was measured by ELISA method. Results: Positive CD38 expression was significantly associated with lower Hb and platelets (p = 0.008 and 0.025 respectively) also with higher Beta2 microglobulin (p = 0.012). Soluble HLA G was positively correlated with the platelets count(r = 0.400, p = 0.02). Higher level of soluble form HLA-G was significantly more frequent in patients of 60 years or older (p = 0.001). The cumulative overall survival was 83.3%. Positive CD 38 expression was associated with significantly worse survival (p < 0.005). HB count < 10 gm/dl was associated with significantly worse survival (p < 0.001). Conclusion: CD38 expressions are considered powerful prognostic markers in predicting overall survival for Egyptian CLL patients and they should be assessed to decide the patient's therapy and to determine disease prognosis. Expression of soluble form of HLA-G in CLL patients by ELISA get no extra prognostic importance.

Background: Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in adults presenting with varied clinical course. There is a higher request for founding known prognostic factors for stratifying CLL patients. HLA-G is a non-classical major histocompatibility complex (MHC) molecule. It can be expressed in membrane bound (m.HLA-G) and soluble forms (s.HLA-G). Objective: The aim of work was to investigate the expression of membrane form of HLA-G in CLL and correlate findings and a variety of clinical and laboratory variables. Patients and methods: This prospective study included a total of thirty newly diagnosed B-CLL patients, attending at Hematology Unit, Medical Oncology Department, national Cancer institute, Cairo. This study was conducted between December 2017 to July 2019. Diagnosis of CLL was confirmed by flow cytometric immunophenenotyping using standard lymphoma panel, membrane HLA-G was determined by flow cytometry. Results: The expression of HLA-G by flowcytometry was negatively correlated with the platelet count (r = -0.516, p = 0.004) and Hb (r = -0.479, p = 0.007). The expression of HLA-G was significantly higher in CD38 positive cells (p = 0.006). The expression of HLA-G was significantly higher in Rai stage 4 compared to stage 1 & stage 2 (p = 0.001). Conclusion: It could be concluded that expression of HLA-G might represent signs of immunosuppression in CLL patients which contribute to the immune escape of tumor cells. In addition, HLA-G expression by B-CLL cells correlates significantly with the known prognostic markers of disease progression, mainly Rai clinical staging, CD38 expression and worse survival, making this parameter possibly an important prognostic factors of disease progression.

Following gene expression profiling which compared the two well established prognostic markers in CLL, ZAP-70 and CD38 with unmutated and mutated IgVH, ZAP-70 has emerged as the most promising surrogate marker for the IgVH mutation status. CD38 expression has also been suggested as a surrogate marker for the IgVH mutation status.We aimed to investigate the impact of ZAP-70 and CD38 expressions as well as their combined expressions on the treatment outcome and survival of our CLL patients.This study included 50 CLL patients as well as10 normal volunteers as a control group. All patients were subjected to complete work up and immunophenotyping to confirm the diagnosis. ZAP-70 and CD38 expressions were studied in (CD19+, CD5+) B cells. Results were expressed as percent expression and mean flourecent index (MFI). Results were correlated to the treatment outcome and survival as well as to other prognostic markers of CLL including TLC, Hb level, platelets count, modified Rai staging at diagnosis, P53 and BCL 2.A significant association was found between ZAP-70 percent expression and the diffuse pattern of bone marrow infiltration (p0.002) as well as the P53 percent expression (p=0.005). A Significant increase in serum levels of LDH and B2M in ZAP-70 positive as compared to negative groups was detected (p=0.049 and 0.007 respectively). A higher number of non-responding patients was reported in the ZAP70 positive as compared to ZAP70 negative group (p0.001). ZAP-70 percent expression was significantly associated with shorter time to disease progression (TDP) and shorter overall survival (p=0.025 and 0.029 respectively). A significant increase in serum levels of B2M in CD38 percent positive as compared to negative group was encountered (p=0.045). CD38-MFI showed a significant associations to advanced modified Rai staging at diagnosis (p=0.019) and to higher serum levels of both LDH and B2M (p=0.03 and 0.05 respectively). CD38, either expressed as a percentage or as MFI, showed a significant association with the non-responders (p=0.034 and 0.006 respectively). There was a significant inverse relation between CD38 expression and time to disease progression (p=0.033) while no significant relation was encountered with overall survival (p=0.197). Combined expression of both markers, ZAP-70+ /CD38+ was reported in 5 patients (10%) while ZAP-70- /CD38- expression was encountered in 24 patients (48%). Patients with either ZAP-70+ or CD38+ represented 42% of the cases (21 patients).There were significant differences between the three groups and the initial response to chemotherapy (p=0.001) and the pattern of bone morrow infiltration (p=0.015), while no significant relation was found with age, sex, modified Rai staging at diagnosis or BCL2 percent expression. Patients with combined expression of ZAP-70 and CD38 had significantly shorter TDP and overall survival (p0.001 and 0.03 respectively).ZAP-70 is one of the most important prognostic markers in CLL, it appears to be more predictive of disease progression and poor outcome than CD38 expression. Semi quantification of the CD38 antigen by flowcytometry greatly improves the prognostic value of its expression. The combination of ZAP-70 and CD38 increases the prognostic power of either alone.CLL - Prognostic factors - ZAP 70 and CD38.