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- Day 02
University of Saskatchewan, Canada
Mark Podberezin completed his Medical School (MD) Degree in Russia where he practiced Clinical Hematology before moving to USA. He performed his PhD project in Immunohematology in United Kingdom. After moving to USA, he completed his Anatomic and Clinical Pathology Residency, as well as Surgical Pathology Fellowship training at University of Illinois at Chicago/Cook County Hospital and later completed Hematopathology Fellowship at Texas Methodist Hospital in Houston. Currently, he is Anatomic Pathologist/Hematopathologist and Assistant Clinical Professor at University of Saskatchewan, Canada.
We describe an unusual case of multiple myeloma (MM) with plasmablastic morphology in a young man who, after chemotherapy and autologous stem cell transplant, developed disease recurrence with isolated CNS involvement. Plasmablastic type is characterized by immature cells with round nuclei, prominent central nucleoli, and amount of cytoplasm much smaller than that in mature plasma cell. According to different studies, plasmablastic MM may account for 15-30% of MM cases and tend to be associated with adverse prognosis. It has been shown to correlate with high proliferation rate, extensive bone marrow infiltration, but not with high risk chromosomal aberrations. Despite the fact that plasmablastic morphology is not uncommon in MM patients, CNS involvement in this disease is very rare. Overall, extramedullary involvement is found in 7% of patients with MM upon initial diagnosis, with CNS involvement occurring in less than 1% of patients. Based on Mayo Clinic study of 4060 MM patients, only 0.7% of all patients had CNS disease. MRI studies demonstrate that predominant pattern of CNS myelomatous disease is leptomeningeal involvement, with intraparenchymal tumor-like lesions being much less common. In some patients, dural involvement and/or direct extension of MM into CNS were described. In 82% of patients with CNS myelomatosis, neoplastic plasma cells were found in CSF, and in those without CSF involvement, the diagnosis was made by MRI which detected either leptomeningeal or intraparenchymal involvement. It is worth to mention that CNS involvement in MM tends to occur in younger patients, without evidence of advanced disease, sometime with isolated CNS involvement. In many of these patients, complete remission can be achieved with the use of systemic, rather than intrathecal, chemotherapy, particularly with addition of novel agents such as Bortezomib (proteasome inhibitor) and Lenalidomide (immunomodulatory agent). Diagnostic approach, as well as management of patients with CNS involvement by MM, will be discussed.
Molecular Pathology Laboratory Network, Inc., USA
Bevan Tandon, MD is board certified by the American Board of Pathology in both Hematologic Pathology and Molecular Genetic Pathology. His Hematopathology training was completed at the University of Pittsburgh under the guidance of WHO lead Author, Steven Swerdlow. His Molecular Pathology training at Washington University in St. Louis was focused on next generation sequencing for clinical testing in Oncology. He has multiple publications in the peer reviewed literature including the International Journal of Laboratory Hematology and Modern Pathology. He currently serves as the Director of Clinical Molecular Diagnostics at Molecular Pathology Laboratory Network, Inc., USA.
Next generation sequencing (NGS) methodologies are emerging as an extremely valuable adjunct in the clinical diagnostic evaluation of hematologic cancers. Simultaneous assessment for prognostic or therapeutically predictive mutations across numerous disease relevant genes can be easily accommodated by clinical targeted NGS panels, facilitating significant reductions in labor, cost, and turnaround time for clinical reporting. Multiplex targeted NGS panels also eliminate reliance upon cascaded mutation testing algorithms often found to be highly complex and cumbersome for ordering physicians. Thus, extended mutational profiling using NGS may show significant utility in the evaluation of acute myeloid leukemias and myeloproliferative neoplasms. Targeted NGS gene panels have also been reported to show potential, emerging significance in evaluation of myelodysplastic syndromes, one of the most common clinical indications for bone marrow biopsy. In the setting of acute leukemias and mantle cell lymphoma, minimal residual disease (MRD) testing by NGS has also been reported to show significant improvements in sensitivity and specificity compared to the standard reference methodologies including flow cytometry and PCR. Lastly, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) is the most common leukemia diagnosed among adults in western countries and is associated with heterogeneous clinical outcomes. Somatic hyper mutation status of the IGH gene is one of the most important prognostic biomarkers for risk stratification and guidance of therapy in this setting, and NGS confers significant practical and technical advantages over the current gold standard Sanger Sequencing based approach.
Cardiff University, United Kingdom
Dipak Ramji received his BSc (Hons) degree (Biochemistry) and his PhD from University of Leeds. This was followed by post-doctoral research at the EMBL (Heidelberg) and IRBM (Rome) with fellowships from the Royal Society and the EU. He joined Cardiff University in 1992 and is currently a Reader at Cardiff School of Biosciences. His research is focused on understanding how the immune and inflammatory responses regulate macrophage processes in atherosclerosis with the goal of attaining deeper mechanistic insight and identifying preventative/therapeutic agents. He has published over 80 peer-reviewed papers, reviews and book chapters (h-index = 30; i10-index = 57). He is an Editorial Board member of 16 international journals.
Atherosclerosis, an inflammatory disorder of medium and large arteries and the underlying cause of myocardial infarction and cerebrovascular accident, is responsible for more deaths worldwide than any other disease. Pharmaceutical intervention together with lifestyle changes have recently resulted in a slight reduction in morbidity and mortality from atherosclerosis and its complications, at least in the western world. However, this is expected to change in the future because of global increase in risk factors such as obesity and diabetes. Current pharmaceutical therapies against atherosclerosis such as statins are not fully effective and associated with several side effects together with patient-dependent efficacy. Unfortunately, many pharmaceuticalleads against established targets have proved disappointing at the clinical level (e.g. inhibitors against cholesterol ester transfer protein). It is therefore essential that further research is carried out into alternative therapies for the prevention and/or treatment of atherosclerosis. Nutraceuticals have recently received substantial interest for the prevention/treatment of atherosclerosis (see our article in Nature Reviews Cardiology 13, 2016, 513-32). However, more in-depth understanding is required on the molecular mechanisms underlying the actions of nutraceuticals together with large clinical trials testing their efficacy.We have recently initiated studies on the effects of many nutraceuticals, including certain omega-6-fatty acids, polyphenols and flavanols, on several key monocyte/macrophage processes associated with atherosclerosis in vitro(e.g. monocytic migration, macrophage polarization, foam cell formation, activation of inflammasome and production of reactive oxygen species) and various risk factors in vivo. These will be presented in the context of current therapies and those that are being developed.
Leyla Bahar, after graduating from Cukurova University Faculty of Medicine, she worked as a medical practitioner in Mersin until 2002. In Department of Histology-Embryology she completed PhD in Mersin University Faculty of Medicine in 2008. She has published more than 20 papers and announcement in journals and has been serving as a consultant editor and editorial board member of reputable. Leyla Bahar still continues to work as a scientist and an assistant professor at Mersin University who is working on many issues and as peer-review in journals.
Colorectal cancer (CRC) arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes. The molecular changes occurring during the development of the tumor must be investigated in order to understand the carcinogenesis. The cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, catalyze the formation of prostaglandins, thromboxane, and levuloglandins. COX-2 is induced by inflammatory and mitogenic stimulants and prevails on tumor carcinogenesis by increasing the prostaglandin synthesis in inflammatory and neoplastic tissues. The aim of this study was to investigate the association the COX-2 gene -1195 A>G polymorphism and CRC risk. We also investigated the relationship between the COX-2 gene mRNA levels in peripheral blood monocytes and -1195 A>G polymorphism in CRC. Ninety individuals with CRC and 106 healthy individuals are included in our study. The genotypes are determined by using PCR-RFLP. RNA of individuals with CRC is isolated and RT-PCR is applied. Genotype distribution and allelic frequencies for -1195 A>G polymorphism of COX-2 gene weren’t significantly different between patients and controls. COX-2 gene mRNA levels and genotype distributions of this polymorphism no difference between CRC patients and controls. While one of the other factors of developing CRC; the advanced age and male gender increases the risk of developing CRC, BMI, smoking and alcohol intake have no affect on risk of developing CRC. Our study is the first study to investigate the relation between -1195 A>G polymorphism and mRNA levels of COX-2 gene in CRC in Turkish population.
University of Mersin, Turkey
Nazan Eras; after graduate from Dicle University Faculty of Medicine, she worked as a general practitioner. She completed her MSc in 2006 and PhD in 2012 at Mersin University Faculty of Medicine, Department of Molecular Biology and Genetics. She has been serving as peer reviewer in journals. Nazan Eras still continues to work as scientist and assistant professor at Mersin University Medical Faculty, Department of Medical Genetics. Her research interests include clinical cancer genetics, human molecular genetics and oxidative stress.
For understanding of leukemia and treated with early diagnosis, it should be investigated moleculer changes that occur during the development of leukemia. Apoptosis is central to the development and homeostasis of the hematopoietic system. Previous studies have reported that leukemia cells invariably have abnormalities in one or more apoptotic pathways. The current study investigated the relationship between polymorphisms of caspase 3 G>T rs4647601 and caspase 9 A>G rs4645978 and leukemia. Besides that we aimed to determine caspase 3 and caspase 9 enzyme levels possible effects on the risk of developing leukemia. The case group consisted of 100 patients (mean age:56±03) who had been newly diagnosed with leukemia at the Department of Hematology, Mersin University Faculty of Medicine, Turkey. The control group comprised of 100 healthy properly age and sex matched individuals (mean age:54±15) with a no history of leukemia. The genotypes detected by using Real-Time PCR. We measured enzyme levels of caspase 3 and 9 in serum which obtained from blood samples. No significant association was observed between caspase 3 G>T rs4647601 and caspase 9 A>G rs4645978 polymorphisms and leukemia. We found that median levels of caspase 3 and 9 were higher in leukemias than in normal blood cells (P <0.001). This is the first study reporting the detailed distribution of alleles and genotypes of caspase 3 and caspase 9 in leukemia patients in Turkish population. Taken together, we conclude that caspase 3 and caspase 9 levels may useful for the early diagnosis of leukemia.