الفهرس 
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Abstract
Multiple Myeloma (MM) is a malignant neoplastic disease characterized by uncontrolled proliferation of plasma cells in the bone marrow and production of monoclonal immunoglobulins that comprise 1% of all malignancies and 10-15% of all hematological malignancies. It is a major cause of cancer mortality and considered the second most frequent hematological malignancy in Europe. The clinical manifestations of MM include hypercalcemia, renal failure, anemia, lytic bone lesions and immunodeficiency. Interferon Gamma Inducible Protein 16 (IFI16) is belonging to IFN – inducible Pyrin and hematopoietic interferon – inducible nuclear (HIN) domain containing protein (PYHIN – 200) gene family encoding evolutionary related proteins that share a 200 – amino acid signature motif, HIN which modulates proliferation, survival and differentiation of different cell lineages. IFI-16 is regulated during the differentiation of B cells and was associated with the expression of genes involved in interferon response, cell cycle, cell death and proliferation and, interestingly, lipid and glucose metabolism, suggesting that IFI16 deregulation might be associated with relevant changes in cell biology. IFI16, normally expressed in cell nuclei, may be overexpressed, mis localized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders. Several studies have shown that IFI16 predicted prognosis in many cancers Also, enhanced IFI16 expression was reported to be associated with good prognosis of hematological malignancies, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma as a cancer suppressor. However, the relationship between MM prognosis and IFI16 expression is still a subject of interest. This work aims to study the serum level of IFI-16 in newly diagnosed multiple myeloma patients, and its relation to patient’s prognosis. This prospective study was conducted on 60 subjects divided into 2 groups: group I (Patients group): 30 newly diagnosed multiple myeloma patients presenting to Hematology Unit, Internal Medicine Department, Tanta University Hospital. group II (Control group): 30 healthy volunteers matched in age and sex with the patients group Our results were summarized as follow: • 27 (90%) patients had anemia, 20 (67%) patients had renal impairment and 16 (53.3%) patients had Lytic bone lesion. • According to Durie-Salmon staging system of MM patients, 5 (16.67%) patients were in Stage I, 13 (43%) patients were in Stage II, 12 (40%) patients were in Stage III. • Hb level was significantly decreased in the patients group than the control group (P value <0.001) • WBCs count was significantly decreased in the patients group than the control group (P value <0.001). • PLTs count was insignificantly different between the studied groups. • Blood urea and serum creatinine were significantly increased in the patients group than the control group (P value <0.001). • Liver enzymes (ALT&AST) were significantly increased in the patients group than the control group (P value =0.011&0.010) respectively while albumin was significantly decreased in the patients group than the control group (P value <0.001) • Calcium, LDH and β2 microglobulin were significantly increased in the patients group than the control group (P value < 0.001) • SPEP showed that M band concentration ranged from 3.18-7.5 g/dL with a mean ± SD of 5.30±1.23 g/dL. • Serum immunofixation showed that, 15 (50%) patients had IgG Kappa, 6 (20%) patients had IgG Lambda, 4 (13%) patients had IgA Lambda and 5 (17%) patients had IgA Kappa. • Plasma cell in BM in MM patients at time of diagnosis ranged from 29 to 88% with a mean ± SD of 43.05±15.54%. • IFI16 level was significantly increased in the patients group than the control group (P value =0.005). • IFI-16 level in different stages showed that the mean ±SD of IFI16 was 1.38±1.19 in stage I, 1.28±0.41 in stage II, and was 2.63±1.04 in stage III. There was a statistically significant difference among three stages of multiple myeloma. • IFI-16 was significant positively correlated with Serum Creatinine level, LDH, β2 microglobulin and Ca with p value (0.011, 0.013, 0.023,0.014) respectively while negatively correlated with albumin with p value = 0.004. While no significant correlation was observed between IFI16 and Hb level, M band concentration, Plasma cell percentage and PLTs count. • Using Roc curve, IFI16 can significantly diagnose multiple myeloma (AUC= 0.701, P value =0.003) at cut off >1.43, 66.67% sensitivity, 63.33% specificity, 64.5% PPV and 65.5% NPV. • IFI-16 was significantly increased in relapsed cases than non-relapsed cases Mean±SD 3.40 ± 0.94 &1.55 ± 0.73 respectively (P.value < 0.001). • Using Kaplan-Meier survival curve for DFS showed that patients with high IFI-16 (above median) had a shorter DFS compared to those with low IFI-16 (below median), Mean 7.200&9.0 respectively.