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The Impact of miRNA-155 Expression on Treatment Outcome in Adult Acute Myeloid Leukemia Patients

Journal of Cancer Therapy 2019年第3期10卷 203-214页

作者： Tarek Elgohary Fouad Abu-Taleb rania ghonaim Medical Oncology and Hematology Department Zagazig University Hospitals Zagazig Egypt Moussat Hospital Dammam Saudi Arabia Clinical Pathology Department Zagazig University Hospitals Zagazig Egypt

Background: Acute myeloid leukemia is a heterogeneous hematologic malignancy associated with gene mutations, chromosomal rearrangements, deregulation of gene expression and epigenetic modifications. The treatment outcome of AML is highly variable signifying the heterogeneous nature of the disease. Aim of the Study: To evaluate miRNA-155 expression level as a prognostic marker for adult patients with acute myeloid leukemia. Patients and Methods: 101 subjects were included in this study. They were classified into 2 groups, patient group (61 adult patients with newly diagnosed acute myeloid leukemia) and control group (40 apparently healthy adult subjects). miRNA-155 expression was assessed using real time PCR using QIAGEN, miScript, Quanti Tect and Rotor-isc (QIAGEN Group) PAXgene (pre Analytix Gmbh). Samples were either peripheral blood or bone marrow aspiration sample. Results: Roc curve detected 2.85 as best fit value of miRNA-155 for discriminating patients from healthy controls with sensitivity 92.3%, specificity 88.5%, AUC 0.98 and CI (0.96 - 0.99) (p < 0.001). The 75th percentile value of the patient group was taken as prognostic cut off value with a value < 9.8 as low miRNA-155 and a value ≥ 9.8 as high miRNA-155. The expression level of miRNA-155 was significantly higher in AML patients than in controls (p = 0.002). Patients with high miRNA expression had a significantly higher white blood cells count (p = 0.002), bone marrow blasts (p = 0.006) and peripheral blood blasts (p = 0.006) compared to patients with low miRNA-155 expression. Patients with poor cytogentics had a significantly higher level of miRNA-155 expression compared to patients with favorable cytogentics (p = 0.007). The complete remission rate was significantly higher in patients with low miRNA-155 expression compared to those with high expression (86.4% and 23.5%, consequently, p = 0.004). The disease free survival was significantly shorter in patients with high miRNA-155 expression compared t

关键词： miR-155 Micro-RNA AML

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Study of Minimal Residual Disease in Adults with B-Lineage Acute Lymphoblastic Leukemia by Flowcytometry

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Journal of Cancer Therapy 2017年第4期8卷 386-398页

作者： rania A. ghonaim Tarek A. Elgohary Department of Clinical Pathology Faculty of Medicine Zagazig University Zagazig Egypt Department of Medical Oncology & Hematology Faculty of Medicine Zagazig University Zagazig Egypt

Background: After achieving morphological remission, existence of few number of leukemic cells in the patient’s blood represents the minimal residual disease (MRD) and its monitoring helps in evaluating early treatment response and future relapse. Patients and methods: Eighty seven newly diagnosed (B-ALL) cases were enrolled in the present study in the time period from October 2013 to October 2016. A panel of 4 monoclonal antibodies (CD10FITC, CD19PE, CD34PercP and CD45APC) were defined at diagnosis and after morphological remission for tracing of minimal residual disease (MRD). Results: Eighty seven newly diagnosed B-ALL cases were included in the present study of which 73 (84%) showed positive expression to CD45 in combination with (CD10, CD19 and CD34) at diagnosis, which allow us to use this combination for further assessment of MRD after morphological remission. In our study 65% of patients had negative MRD ( Conclusion: MRD detection by flow cytometry using the combination of CD45 with CD10, CD19 & CD34 is an easy and reliable method. Patients with positive MRD are at higher risk of relapse and have inferior overall survival rates compared to those with MRD-ve. Future studies focusing on treatment intensification for the group of patients with +ve MRD aiming to improve the treatment outcome are warranted.

关键词： Acute Lymphoblastic Leukemia (ALL) Minimal Residual Disease (MRD) Flowcytometry (FCM) Complete Response (CR) Disease Free Survival (DFS) Overall Survival (OS)

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The Prognostic Value of Vitamin D Insufficiency &Vitamin D Receptor Gene Polymorphism in Adult Acute Myeloid Leukemia Patients

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Journal of Cancer Therapy 2019年第5期10卷 361-370页

作者： Amal Zidan Alaa Omran rania ghonaim Fouad Abu-Taleb Tarek Elgohary Clinical Pathology Department Zagazig University Hospitals Ash Sharqiyah Egypt Medical Oncology and Hematology Department Zagazig University Hospitals Ash Sharqiyah Egypt Mouwasat Hospital Dammam City Saudi Arabia

Background: Vitamin D regulates many aspects of cellular growth and differentiation in normal and cancer cells. There is growing evidence for both serum vitamin D level and VDR gene polymorphism as prognostic factors in hematologic malignancies. Aim of this work: Evaluation of vitamin D serum level and VDR FOKI polymorphism as prognostic factors in adult AML patients. Patients & Methods: Eighty subjects were included in this study, 50 adult patients with newly diagnosed AML and 30 apparently healthy controls matched for age and sex. Venous blood samples were withdrawn from all subjects for measurement of serum 25(OH) vitamin D using competitive photo chemiluminescence and molecular detection of VDR (FOKI) polymorphism, which was done by RFLP PCR. All patients received the standard induction chemotherapy regimen 3 & 7. Results: The rate of vitamin D insufficiency was significantly higher in AML patients compared to controls (58% vs 16%, p = 0.03). The mutant FOKI genotype (FF & Ff) was found in 52 % of patients compared to 23 % of controls (p = 0.02). Patient with sufficient vitamin D level showed a significantly higher complete response rate compared to those with insufficient level (90% vs 44%, p = 0.02), while none of the other clinical features showed significant relation. Patients with wild type FOKI polymorphism (FF) were more likely to have favorable cytogenetics, while patient with mutant FOKI polymorphism were more likely to have poor cytogenetics (p = 0.03). The CR rate was highest in the wild type FF group (87.5%) followed by the heterozygous Ff group (50%), while none of the patients in the homozygous ff group achieved CR (p = 0.04). Conclusion: VDR FOKI polymorphism and serum vitamin D level showed a significant impact on the treatment outcome of adult AML patients suggesting their potential role as prognostic factors in these patients. Longer follow up will be needed to study the impact on overall and disease free survival.

关键词： Vitamin D VDR FOKI Polymorphism

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