الفهرس 
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Abstract
Acute myeloid leukemia (AML) is a heterogeneous group of leukemias that arise in precursors of myeloid, erythroid, megakaryocytic, and monocytic cell lineages. These leukemias result from clonal transformation of hematopoietic precursors through the acquisition of chromosomal rearrangements and multiple gene mutations. The FAB classification is still widely used in clinical setting that groups AML into 8 subgroups (M0-M7) based on its degree of differentiation and morphology. Moreover, (WHO) classification for AML added the genetic, immunophenotypic, biological and clinical features to the morphological findings. Immunophenotyping has become an important diagnostic tool in establishing the diagnosis and classification of acute myeloid leukemia. Natural killer (NK) cells are innate lymphocytes that are crucial for the early control of some pathogen infections and malignancies. NK cells kill infected or transformed cells through the release of cytolytic granules that contain perforin and granzymes or through the ligation of death-inducing receptors. An important family of adhesion molecules that bind nectins and nectin-like family proteins has been identified as a crucial regulator of NK cell functions CD226 (also known as DNAM1, PTAl and TLISA1) is the most extensively studied member of this family and was originally described as an adhesion molecule that controls NK cell-mediated cytotoxicity. Its ligands, CD 112 (also known as nectin 2 and PRR2) and CD 155 (also known as PVR and NECL5), are regulated by cellular stress and are involved in different pathological conditions ranging from cancer to infectious disease. CD112 is one of 6 activating NK receptor ligands (NKRLs) (MICA, MICAB, CD155, CD112, ULBP1, and ULBP2/5/6). AML blasts displayed heterogeneous expression of NKRLs., CD112 was most frequently expressed. Several studies hypothesized that patients with blasts expressing NKRLs that facilitated NK cell activation (namely with a low-inhibitory and highactivating ligand expression pattern) would have improved immune surveillance and reduced disease relapse. This Study aimed to evaluate the impact of natural killer cell (CD56+, CD16+, CD3-) and its activating receptor ligand (CD 112) in acute myeloid leukemia and their clinicopathological significance. The current study was carried out on 40 newly diagnosed patients suffering from acute myeloid leukemia. Their ages ranged from 18-65 years they were 24 (60%) males and 16 (40%) female with male to female ratio 1.5:1. In addition to 20 apparently healthy subjects matched for age and sex with patients. They were 14 males (70.0%) and 6 females (30.0%) their ages ranged from 19 to 61years. Patients and controls were subjected to detailed history taking, thorough clinical examination, abdominal ultrasonography, laboratory investigations including: complete blood picture, bone marrow aspiration, cytochemistry, immunophenotyping and flowcytometric analysis of NK cells expression on peripheral blood sample and CD112 expression on bone marrow samples for all patients and control. • The results of the present study showed: • Hepatosplenomegaly and lymphadenopathy was observed in most of newly diagnosed AML patients. • Bleeding was observed in 31(77.5%) and 32 (80.0%) of patients had fever. • Serum LDH was significantly higher in AML patients as compared to control groups. • First hour ESR was significantly higher in AML patients as compared to control groups. • Hb level was significantly lower in AML patients as compared to control group. • Platelets count was significantly lower in AML patients as compared to control group. • WBCs count was significantly higher in AML patients as compared to control group. • Bone marrow blasts were significantly higher in newly diagnosed AML patients as compared to controls. • There was a significant decrease in percentage of NK cells in newly diagnosed AML patients. The percentage of expression of NK cells in AML patients ranged from 2.30 – 35.30 with a median (IQR) of 11.35 (7.1 – 16.1) and in control group from 3.90 – 25.30 with a median (IQR) of 16.25 (13.3 – 18.2). • There was a significant increase in expression of CD112 in newly diagnosed AML patients. The expression percentage of CD112 in AML • patients ranged from 7.10 – 89.10 with a median (IQR) of 53.15 (28.6 – 76.8) and in control group from 3.50 – 28.30 with a median (IQR) of 10.75 (7.45 – 18.80). • There was a significant inverse correlation between NK cells expression level and CD112 expression. • 15 cases (37.5%) had complete remission, 13 cases (32.5%) had relapse attack after the onset of treatment and 12 cases(35%) died during the period of follow up and the duration of the overall survival (OS) and disease free survival ranged from 2.0 – 24.0 months with Mean ± SD of 14.68 ± 8.19 and Median (IQR) of 13.50 (7.0 – 24.0). • By analysis of survival and using Kaplan- meier curve, as regard NK cell it has been found that there was a significant correlation between low levels and high levels of expression of NK cells. Kaplan-Meier survival curve shows a significant higher overall survival in patients with low NK cells expression level with cutoff f15.5. • Also, by analysis of survival and using Kaplan- meier curve, as regard CD112 it has been found that there was a significant correlation between high levels and low levels of expression of CD112. Kaplan-Meier survival curve shows a significant higher overall survival in patients with high CD112 expression level with cutoff >18.2.