APRIL gene expression in a cohort of Egyptian acute myeloid leukemia patients: Clinical and prognostic significance.

APRIL (A Proliferation Inducing Ligand) is a member of the tumor necrosis factor (TNF) family. It is essential for the survival of normal and malignant B lymphocytes. Increased expression of APRIL is noted in most of hematological malignancies and auto immune diseases. We investigated the expression level of APRIL mRNA in 50 de novo acute myeloid leukemia (AML) patients, together with 20 healthy controls using a Real-Time Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RTQ-PCR) with a specific aim of determining its relation to clinical features and laboratory findings at diagnosis and its impact on the response to therapy. APRIL mRNA expression level was significantly higher in AML patients than in controls (p = < 0.001). APRIL expression level was significantly higher in patients who didn't achieve CR compared to those who achieved CR (p < 0.001). Patients who did not achieve CR also had higher TLC, lower platelets and older age than CR patients. The difference was statistically significant (p < 0.001, p = 0.047, p = 0.019) respectively. APRIL levels showed significant positive correlation with TLC (r = 0.743.p < 0.001), with age (r = 0.296,p = 0.037) and a negative correlation with platelets count (r = -0.443,p = 0.001) and no correlation with gender, Hb level, BM blast, HSM or LNs enlargement. Our study has shown that APRIL is overexpressed in AML patients, its level might serve as an indicator for disease progression. APRIL might be an indicator for poor prognosis and treatment resistance in AML patient; therefore, APRIL antagonists may represent a novel therapeutic approach for the treatment of AML.

Vitamin D Receptor (VDR) Gene Polymorphisms (FokI, BsmI) and their Relation to Vitamin D Status in Pediatrics ßeta Thalassemia Major.

Vitamin D is critical for calcium, phosphate homeostasis and for mineralization of the skeleton, especially during periods of rapid growth. Vitamin D Deficiency leads to rickets (in children) and osteomalacia (in adults). Expression and activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D, in which several single nucleotide polymorphisms have been identified especially (FokI, BsmI). In this study serum 25 (OH) vitamin D3 levels were estimated by Enzyme Linked Immunosorbent Assay [ELISA], VDR (FokI, BsmI) gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay [PCR-RFLP].Serum levels of calcium, phosphorus, alkaline phosphatase and ferritin were determined in 50 Pediatrics beta thalassemia major patients and 60 controls. Patients had significantly lower serum calcium (p < 0.001) lower serum vitamin D3 (p < 0.001) with elevated levels of phosphorus (p < 0.001) and alkaline phosphatase than controls (p = 0.04). Of the patients studied, 60 % had vitamin D deficiency (<20 ng/ml), 20 % had vitamin D insufficiency (21-30 ng/ml) and 20 % had sufficient vitamin D status (>30 ng/ml). Patients harboring mutant (Ff,ff) and wild (BB) genotypes were associated with lower serum calcium (p = 0.08, 0.02) respectively, lower vitamin D3 levels (p < 0.001, 0.01) respectively. They were also suffering from more bony complications although the difference was not statistically significant (p > 0.05). In conclusion, these results suggest that the VDR (FokI, BsmI) gene polymorphisms influence vitamin D status, (Ff,ff), BB genotypes had lower vitamin D levels, so they might influence risk of development of bone diseases in beta thalassemia major.

The Role of Type I Insulin Like Growth Factor Receptor (IGF-IR) in Adult and Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: Type 1 insulin like growth factor receptor (IGF-IR) is over expressed in many tumors including hematological cancers. It is a critical signaling molecule for tumor cell proliferation and survival. Data suggest that IGF-IR antibodies can effectively and specifically inhibit cancer cell growth in vitro and in vivo. Blockage of IGF-IR expression could be a promising therapeutic approach for the management of cancer patients. AIM OF WORK: To characterize the expression pattern of IGF-IR gene in malignant lymphoblasts of children and adults suffering from ALL in relation to clinical features at diagnosis. PATIENTS AND METHODS: The expression of IGF-IR was analyzed in 60 patients with ALL, 30 childhood ALL (16 newly diagnosed and 14 in complete remission) and 30 adulthood ALL (15 newly diagnosed and 15 in complete remission) together with 20 normal age and sex matched healthy controls using a Real-Time Quantitative Reverse- Transcriptase Polymerase Chain Reaction (RTQ-PCR) to assess the possible relation, association or correlation between IGF-IR expression and ALL clinical and laboratory features at diagnosis. RESULTS: IGF-IR was expressed in all 60 patients with ALL; the expression levels of IGF-IR were significantly higher in newly diagnosed patients than in patients in complete remission (CR) and controls (p < 0.001). There were no statistically significant differences in the expression of IGF-IR between patients with different clinical and laboratory features. CONCLUSION: IGF-1R seems to play a crucial role in patients with ALL since it is expressed in all ALL cases (adulthood and childhood). Therefore, new therapeutic agents targeting IGF-1R may provide a better chance for those patients. KEY WORDS: IGF-IR - Adult ALL - Childhood ALL - RTPCRT - Prognosis.