الفهرس 
World Health Organization (WHO) ClassificationOnly 14 pages are availabe for public view
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Abstract
Acute myeloid leukemia is a clinically and biologically heterogeneous disease characterized by development of a malignant clone of myeloid cells in the bone marrow with arrest of maturation at blast level that accumulates and dominates on the normal bone marrow activity leading to marrow failure. Although some clinical factors such as age, performance status or a history of prior chemotherapy have been associated with the outcome of patients with AML, the most important factor in predicting the risk of relapse has been chromosomal abnormalities detected at diagnosis. MicroRNAs are small, single-stranded RNAs of 21-23 nucleotides in length. It regulates gene expression post-transcriptionally by either degradation of mRNA or inhibition of translation via binding at the 3’-untranslated region of their target genes. In acute myeloid leukemia (AML), microRNAs are involved in hematopoietic cell differentiation, proliferation, and survival. They have an impact on treatment response and outcome. Different microRNA expression profiles are seen in various cytogenetic groups of AML. MiR-328, are small noncoding RNAs that function as posttranscriptional regulators of gene expression by binding to target mRNAs in a sequence-specific manner. MiR-328 plays an inhibitory role in the proliferation of cancer cell lines and indicated that the suppression of miR-328 expression provides an advantage for tumor growth. MiR-96 are transcribed as 80 nucleotide precursors and subsequently processed by the Dicer enzyme to give a23 nucleotide products. The mature products are thought to have regulatory roles through complementarity to mRNA. The present study was designed to evaluate miR-96, and miR-328 expression and to assess its relation to clinical characteristics in newly diagnosed AML patients and hence its implications in determining the prognosis. This study was conducted on 60 persons who were divided into two groups: group I: included 40 newly diagnosed AML patients with age ranging from 2.5 - 64 years. group II: included 20 apparently healthy subjects as a control with age ranging from 3 - 67 years. All groups were subjected to the following: Full history taking. Thorough clinical examination, laying stress on the presence of extramedullary disease (hepatomegaly, splenomegaly, bleeding tendency, fever and lymphadenopathy). A) Routine investigation: Complete blood picture. Liver function tests kidney function test CRP. LDH. B) Bone marrow examination: (For patients only) Cytochemistry. Immunophenotyping. Cytogenetics. C) Special Investigations: Detection of expression levels of miR-328, miR-96 by SYBR Green Real time PCR in newly diagnosed AML peripheral blood samples and normal group. MiR-96 and miR-328 were found to be significantly down-regulated in plasma of AML patients with median fold change 49.42 and 32.89 respectively compared to the healthy control group. Statistical analysis was done between miR-328, miR-96 and different parameters and showed the following results: MiR-328, miR-96 expression and patients characteristics: No statistical significant difference in miR-328, miR-96 expression was present among different age groups, between males and females or among different FAB subtypes. No statistical significant difference in miR-328, miR-96 expression was present between patients with lymphadenopathy, bleeding tendency, fever splenomegaly and/or hepatomegaly and those with no clinical characteristics at presentation.
Significant Negative correlation was present between miR-328, miR-96 with WBCs count and blast count in PB and BM. However, positive correlation with hemoglobin concentration and platelets counts. Statistically significant difference in miR-328, miR-96 expression among intermediate and unfavorable cytogenetics of AML. Otherwise, no significant correlations were found with favorable cytogenetics of AML patients. MiR-328, miR-96 expression in relation to disease outcome: Statistically significant difference in miR-328, miR-96 expression in relation to response of therapy in relapsed and refractory AML patients. Otherwise, No significant correlations were found with patients achieved complete remission. Mean overall survival of 14 months in AML patients. Overall survival in patients with low miR-96 expression was significantly lower than that in those with high miR-96 expression. MiR-96 at levels less than the median (49.42) were assigned to the low-expression group and those samples with expression equal to or above the median value were assigned to the high-expression group. Overall survival in patients with low miR-328expression was significantly lower than that in those with high miR-328expression. MiR-328 at levels less than the median (32.89) were assigned to the low-expression group and those samples with expression equal to or above the median value were assigned to the high-expression group.