الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Summary
Acute myeloid leukemia (AML), is a neoplasm of the blood and bone marrow which is characterized by the proliferation of clonal neoplastic myeloid hematopoietic precursor cells and impaired production of normal hematopoiesis. AML the most common type of acute leukemia in adults (Min et al., 2018).
Acute lymphocytic leukemia (ALL), is an acute form of cancer of the white blood cells, characterized by the overproduction and accumulation of cancerous, immature white blood cells, known as lymphoblasts. In persons with ALL,lymphoblasts are overproduced in the bone marrow and continuously multiply, causing damage and death by inhibiting the production of normal cells in the bone marrow and by infiltrating to other organs (Balievic et al., 2016).
The Proviral Integration Site For Moloney Murine Leukemia Virus (PIM) kinases are highly conserved serine/threonine kinases that have been implicated in cancer progression and the development of resistance to chemotherapeutic agents. PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance (Noel and Andrew ,2015).
Nuclear factor kappa B (NF-κβ) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κβ is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κβ plays a key role in regulating the immune response to infection (Ting et al., 2017).
The present study is designed to evaluate the value of PIM-2 and NF-κβ gene expression in patients with Acute Myloid Leukemia and Acute Lymphoblastic Leukemia and its association with response rate .
We conducted our study on thirty patients with Acute Myeloid leukemia (AML) and thirty patients with Acute Lymphoblastic Leukemia (ALL), and twenty healthy age and sex matched normal controls . All Patients were subjected to full history taking, full clinical examination and routine laboratory investigations, complete Blood Count (CBC), bone Marrow Examination, cytochemical Stain Studies, immunophenotyping analysis and Specific Laboratory Investigation, detection of PIM-2 and NF-κβ gene expression in peripheral blood mononuclear cells using Quantitative Polymerase Chain Reaction.
In the current study, the expression level of NF-κβ gene was higher in AML patients than in control group. The difference showed statistical significant (p= 0.009). Also the expression level of NF-κβ gene was higher in ALL patients than in control group. The difference showed statistical significant (p<0.001).
The expression level of PIM2 gene was higher in AML patients than in control group. The difference showed statistical significant (p<0.001). The expression level of PIM2 in ALL patients showed no statistically significant difference (p=0.051).
In our study, regarding follow up of AML patients after induction therapy , 16 patient out of 30 AML patient achieved complete remission (53.3%) compared to 14 AML patients (46.7%) who didn’t achieve complete remission .There was a statistical significant difference in follow up regarding overall survival in relation to level of NFκβ gene in AML patients. But there was no statistical significant difference in follow up regarding overall survival in relation to level of PIM2 gene in AML patients.
Regarding follow up of ALL patients after induction therapy , 19 patient out of 30 ALL patient achieved complete remission (63.3%) compared to 9 ALL patients (30%) who didn’t achieve complete remission .There was no statistical significant difference in follow up regarding overall survival in relation to level of NFκβ gene in ALL patients.There was no statistical significant difference in follow up regarding overall survival in relation to level of PIM2 gene in ALL patients.
In Conclusion, in the current study, we found that expression of PIM-2 and NF-κβ genes was significantly increased in patients with AML and ALL, confirming their important role in the pathogenesis of acute leukemias. The high expression of the NFκβ gene was associated with worse overall survival in patients with AML.Similarly, high expression of PIM2 gene was associated with low CR rate and decreased DFS in AML patients. Hence, NFκβ and PIM2 may be valuable new markers in the prognosis of AML patients and could be also regarded as valuable targets in treatment of acute leukemias.