Expression of BCL2L12and LIPOCALIN 2 in Adult Patient with Acute Myeloid Leukemia and Correlation with Clinical Response.

BACKGROUND: Acute myeloid leukemia (AML) is a malignancy arising within the bone marrow (BM), in which leukemic cells proliferate uncontrollably in association with a disruption of normal hematopoiesis.Aim of the work to evaluate the expression of LCN and BCL2L2, in newly diagnosed bone marrow samples from adult with AML and to correlate their expression levels with clinical and Laboratory data of the patients especially that known to have a prognostic feature. METHODS: This study was carried out on 87 consecutive newly diagnosed adult AML patients of which 75 are evaluated for both LCN, BCL2L12 (All 87 are evaluated for LCN). In addition, 20 donors of matched age and sex healthy individuals from donors for bone marrow transplantation were included as a control group. RESULTS: No statistical significant correlation was found between LCN over-expression and the control group , there was no statistical significance between its expression and age, sex, hepatomegally, splenomegally and lymphadenopathy, also there was no statistical significance regarding peripheral blood and bone marrow findings, immunophenotyping, cytogenetics or molecular findings and MRD at day 15.No statistical significance was found between BCL2L12 expression and the control group again there was no statistical significance between its expression and age, sex, hepatomegally, splenomegally and lymphadenopathy, also there was no statistical significance regarding peripheral blood and bone marrow findings, immunophenotyping, cytogenetics or molecular findings and MRD at day 15. CONCLUSION: LCN and BCL2L12 were found to be expressed with non significant difference in AML as in normal subjects; however studies on large number of cases are needed to confirm our finding. The role of LCN and BCL2L12 need to be verified by further large-scale sample and further studies.
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Associations of interleukin-10 gene polymorphisms with acute myeloid leukemia in human (Egypt).

BACKGROUND: Acute myeloid leukemia (AML) is a cytogenetically and molecularly heterogeneous diseases, and characterization of transforming genetic events is becoming increasingly important. Interleukins (ILs) are a diverse set of small cell signaling protein molecules. Single nucleotide polymorphisms (SNPs) of ILs alter their function, increasing susceptibility to different diseases. PATIENTS AND METHODS: We investigated the association between polymorphism in IL-10 -819T/C (rs1800871) and the risk of AML in the Egyptian population. DNA was isolated from bone marrow of 80 newly diagnosed adult AML patients, and 85 age- and sex-matched controls. Genetic analysis of IL-10 SNPs at -819T/C was assayed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Genetic analysis of IL-10 revealed that the Egyptians have high -819T allele frequencies in apparently healthy controls, whereas -819CC genotype and the -819C allele frequencies in the AML group were higher than in the controls (P = 0.000086). The study suggested that subjects carrying the rs1800871CC genotype and C allele had a significantly increased risk for AML. CONCLUSION: IL-10 SNP at -819 was associated with enhanced AML risk, suggesting that rs1800871 provides clue for future studies and early detection of AML.

Expression of Micro-RNA 128 and Let-7b in Pediatric Acute Lymphoblastic Leukemia Cases

Background: MicroRNAs (miRNAs) play important roles in the pathogenesis of leukemia and their altered expression is associated with many types of solid and hematological malignancies. Methods: The study was performed on 70 consecutive newly diagnosed pediatric acute lymphoblastic leukemia (ALL) patients, of which 56 were evaluated for both bone marrow miR-128 and let-7b (all 70 for let-7b) by real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). In addition, seven age and sex matched healthy controls were assessed. Results: miR-128 expression was significantly higher in ALL patients compared with healthy controls (p<0.001). However, the expression levels of let-7b showed no statistical significant difference between the groups. No significant links were noted with clinical details, laboratory data and response to treatment. Conclusion: The results suggest that determination of miR-128 expression level may provide a tool for confirmation of a diagnosis of childhood ALL, follow up for response of treatment and a possible predictor of early relapse. Any role of let-7b in pediatric ALL needs to be further assessed.

The Meningioma 1 (MN1) Gene is an Independent Poor Prognostic Factor in Adult Egyptian Acute Myeloid Leukemia Patients

Aim: To determine the prognostic importance of meningioma 1 (MN1) gene expression levels in the context of other predictive markers for acute myeloid leukemia (AML) cases. Methods: MN1 expression was measured in 85 newly diagnosed adults younger than 60 years by real-time reverse-transcriptase polymerase chain reaction. Results: At diagnosis 67.4% of cases had elevated MN1 expression, this being associated with a worse prognosis, higher incidence of lymphadenopathy and CD34 transcript expression (p=0.02 and <0.001, respectively). No other molecular or clinical characteristics were significantly associated with MN1expression. Patients with high MN1 expression had lower complete response rate at day 15 compared to patients with low MN1 expression (p=0.09) and a significantly higher relapse rate (21.1% versus 7.7%, respectively, p=0.04). Patients with high MN1 expression had shorter TTP compared to those with low expression, p= 0.07. Conclusion: MN1 expression may predict outcome in AML patients. The MN1 gene and micro RNA expression suggest a biological feature that could be used as therapeutic targets.

Association of CYP3A5*3 and CYP1A1*2C Polymorphism with Development of Acute Myeloid Leukemia in Egyptian Patients

Aim: Cytochrome P450 (CYP) enzyme catalyzes the phase I metabolism reaction which metabolize endogenous and exogenous DNA-reactive chemical compounds and xenobiotics which could induce genotoxicity and increase the risk for leukemia. We aimed to detect frequency of CYP3A5*3 and CYP1A1*2C polymorphisms in Egyptian acute myeloid leukemia (AML) patients and to determine role of allele's variants as a risk factor for developing leukemia. Patients and Methods: A case-control study was conducted on seventy acute myeloid leukemia patients and thirty control subjects. Samples were analyzed for prevalence of CYP3A5*3 and CYP1A1*2C polymorphisms using PCR - restriction fragment length polymorphism method. Results: CYP3A5*3 polymorphism (3/3) and (1/3) genotype were significantly elevated in AML group compared to control group (p=0.002). However, no statistical significant differences were found between patients and control group as regard CYP1A1*2C polymorphism. Conclusion: Our results suggest that Egyptians carrying CYP3A5*3 polymorphism might have an increased risk of AML emphasizing the significance of effective phase I detoxification in carcinogenesis.

Significance of Some Proliferation Markers and Some Prognostic Factors in Patients with Multiple Myeloma and their Impact on the Patients' Survival.

BACKGROUND: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6, IL10 are known to influence the growth and survival of the malignant clone. AIM: The objectives of the present study were to investigate the circulating levels of BAFF , IL-10 and IL-6 , correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on the patients' survival. MATERIALS AND METHODS: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups. Survival analysis was performed for all patients. RESULTS: Studied markers were higher in the MM patients compared to the normal control subjects. Patients' survival was improved by high serum BAFF levels. CONCLUSIONS: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

Significance of Proliferation Markers and Prognostic Factors in Egyptian Patients with Multiple Myeloma.

BACKGROUND: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6 and IL10 are known to influence the growth and survival of malignant clones. AIM: The objectives of the present study were to investigate the circulating levels of BAFF , IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on patients' survival. MATERIALS AND METHODS: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups and survival analysis was performed for all patients. RESULTS: Studied markers were higher in the MM patients compared to the normal control subjects. Patients survival was improved by high serum BAFF levels. CONCLUSIONS: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

Prognostic Value of a CYP2B6 Gene Polymorphism in Patients with Acute Myeloid Leukemia.

BACKGROUND: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. MATERIALS AND METHODS: DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression- free survival (PFS) (p-value=0.245). CONCLUSIONS: Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.