Prognostic Impact of IL17 A Gene Polymorphismson Egyptian Patients with Multiple Myeloma.

INTRODUCTION: Multiple myeloma (MM) is a B-cell lymphoproliferative disease in which the bone marrow microenvironment plays an important role in pathogenesis. The T helper (Th-17) cell plays an important role in the development of cancer by releasing pro-inflammatory cytokines such as IL-17A and IL-17F. Th-17 cells have been studied in a variety of solid tumors, as well as few hematological malignancies, including acute myeloid leukemia, non-Hodgkin lymphoma, and monoclonal gammopathy of unknown significance. AIM: Our study aimed to assess the association between IL-17A polymorphism and MM risk and other MM characteristics in Egyptian patients. PATIENTS & METHODS: a prospective study involving 77 patients with MM (mean age 54.6 years; males 53.2%; females 46.8%) and a healthy control group of same age and gender. It was performed at the Mansoura University Oncology Center (OCMU). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach was used to detect IL17A 197 G/A (rs2275913) genotypes in genomic DNA from MM patients and healthy controls. RESULTS: The IL-17A polymorphism may not be associated to myeloma predilection in the Egyptians as a whole. There was also no significant correlation in statistical study between gender and the IL-17A polymorphism. (p 0.14), a number of clinical and laboratory characteristics, including hypercalcemia (p 0.28), hypoalbuminemia (p 0.49), renal impairment (p 0.13), high LDH (p 0.62), osteolytic bone lesions (p 0.26), and pathological fracture (p 0.96), are also present. Nevertheless, no statistically significant difference in the OS of MM patients was detected for the IL-17A polymorphism (p 0.83). CONCLUSION: Our research demonstrated that IL-17A polymorphism may not be linked to multiple myeloma susceptibility in our population and did not influence its different clinical and laboratory features. IL-17A polymorphism had no effect on OS in MM patients.

Prognostic role of TNF alpha, LT alpha, MDR1 and codon 72 Tp53 gene polymorphisms on multiple myeloma Egyptian patients.

Multiple Myeloma (MM) is a type of hematologic malignancies that characterized by uncontrolled plasma cell proliferation. So, the diagnosis depends on the increased numbers of abnormal, immature, or atypical plasma cells in the bone marrow, and many patients present with laboratory abnormalities, such as anemia, hypercalcemia, renal disease, and high protein levels in blood and urine. We aim to analyze the association of some genetic polymorphisms and its effect on the overall survival (OS) among MM patients. SUBJECTS AND METHODS: We analyzed TNFα 308 G/A, TNFα 238 G/A, LTA252A/G, MDR 3435 C/T, MDR 1236 C/T, TP53 Arg72Pro in 110 multiple myeloma case and 112 healthy controls. The genotyping was performed using PCR-RFFLP. RESULTS: In TNF308 AA genotype and A allele were significantly lower with protective effect against MM development (OR=0.318, 0.742) respectively. LTA 252, GG genotypes had lower frequency in MM cases compared to control group with protective effect against MM development (OR=0.361). In TNF238, MDR1 3435 C/T, TP53 codon 72 polymorphism we didn't find any statistically significant relation between MM and control groups. In Uni and multivariant analysis show ISS, IgG, TP53 Arg72ProGC+CC as risk predictors of shorter OS.But TNFα-308 GA+AA and LTA 252 AG+GG were considered as predictors of longer OS in MM cases. CONCLUSION: Our result confirms the association of TNF-308, LTA and TP53 codon72 with prognostic outcome in MM. As a result, we suggest involving these genes as a biomarker test to predicts the risk and prognostic outcome of MM. Also, we recommend further investigations of these polymorphisms in MM especially LTA and TP53codon 72 polymorphism which have very low reported studies. MICROABSTRACT: Many genes can affect the prognosis of MM. We analyzed some of them in 110 MM and 112 controls using PCR-RFLP. TNFα-308 AA and LTA-252 GG had lower frequency while MDR1-1236 TT had higher frequency in MM. TNFα-308 AA and LTA-252 GG were significantly associated with higher OS but TP53 codon72 polymorphism CC with lower OS. These findings confirm the association of these genes with prognostic outcome in MM.

JAK2, CALR, and MPL Mutations in Egyptian Patients With Classic Philadelphia-negative Myeloproliferative Neoplasms.

BACKGROUND: Genetic mutations have been proven to be one of the major criteria in the diagnosis and distinction of different myeloproliferative neoplasm (MPN) subtypes. Therefore, the aim of this study was to determine the molecular profile of Egyptian patients with MPN subtypes and correlate with clinicopathological status. METHODS: A series of 200 patients with MPNs (92 polycythemia vera, 68 essential thrombocythemia, and 40 primary myelofibrosis) were included in this study. DNA from each sample was amplified using polymerase chain reaction to detect Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) mutations. Sanger sequencing was used to determine the mutation types. RESULTS: Of the 200 samples, 44% had JAK2V617F and 10% were carrying CALR mutation with type 2 being the most frequent type in this study (55%). No MPL or JAK2 exon 12 mutations were detected. All clinical and hematological data had no differences with other populations except that our CALR-positive patients showed a decrease in the platelet count compared with JAK2V617F-positive patients. CONCLUSION: Our study on Egyptian patients shows a specific molecular profile of JAK2 mutation, and CALR mutation type 2 was higher than type 1.