Genetic Alterations, DNA Methylation, Alloantibodies and Phenotypic Heterogeneity in Type III von Willebrand Disease.

Type III von Willebrand disease is present in the Punjab province of Pakistan along with other inherited bleeding disorders like hemophilia. Cousin marriages are very common in Pakistan so genetic studies help to establish protocols for screening, especially at the antenatal level. Factors behind the phenotypic variation of the severity of bleeding in type III vWD are largely unknown. The study was conducted to determine Mutations/genetic alterations in type III von Willebrand disease and also to determine the association of different mutations, methylation status, ITGA2B/B3 mutations and alloimmunization with the severity of type III vWD. After informed consent and detailed history of the patients, routine tests and DNA extraction from blood, mutational analysis was performed by Next Generation Sequencing on Ion Torrent PGM. DNA methylation status was also checked with the help of PCR. In our cohort, 55 cases were detected with pathogenic mutations. A total of 27 different mutations were identified in 55 solved cases; 16 (59.2%) were novel. The mean bleeding score in truncating mutations and essential splice site mutations was relatively higher than weak and strong missense mutations. The mean bleeding score showed insignificant variation for different DNA methylation statuses of the VWF gene at the cg23551979 CpG site. Mutations in exons 7,10, 25, 28, 31, 43, and intron 41 splice site account for 75% of the mutations.

Complete Molecular Response in Chronic Myeloid Leukemia After Six Months of Imatinib: A Single Center Experience.

INTRODUCTION: The hallmark of chronic myeloid leukemia (CML) is the development of the fusion gene, BCR-ABL which has unopposed tyrosine kinase activity. The first tyrosine kinase inhibitor (TKI) imatinib is claimed to have superior efficacy and side effect profile as compared to traditional treatment options. This study was conducted to see our patients' molecular response to imatinib treatment. The objective of this study was to determine the frequency of complete molecular response in patients after six months of imatinib therapy. METHODS: A descriptive case series was designed and conducted in Oncology department, Jinnah hospital Lahore (May-November 2016). Newly diagnosed patients of CML aged between 20 and 65 years were enrolled. They were prescribed 400 mg imatinib daily and complete molecular response was assessed after six months of treatment. RESULTS: Mean age was 39.76 ± 9.072 years. Some 66 of them were males while 69 were females. Some 40 patients (29.6%) were found to be in complete molecular response after six months of imatinib therapy. CONCLUSION: Imatinib at a dose of 400 mg/day is optimal as the primary therapy for CML.