Keynote Forum. Hematologists Day 1. conferenceseries.com. 5 th World Hematologists Congress. 622 th Conference. August 18-19, 2016 London, UK

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2 C D Atreya, 2016, 7:4 (Suppl) C D Atreya U S Food and Drug Administration, USA MicroRNAs in stored blood cells: What future do they hold in transfusion medicine? The discovery that human blood and cellular blood components, especially the packed red cells and platelet concentrates collected from healthy volunteers can be stored ex-vivo for future use in patients undergoing surgery and bleeding trauma has translated into the so called blood bank industry. This very concept has revolutionized the health care by allowing for a managed supply of transfusion quality blood products. During storage, red cells and platelets undergo a series of physiological changes that affect the product quality, which often interferes with the safety and efficacy of such products. This often leads to adverse outcomes in transfused patients. Despite continuous efforts to enhance the product quality, there is still room for improvement for in-vitro standard markers of measurable characteristics that can predict in-vivo safety and efficacy (i.e., biomarkers) in recipients following transfusion. In the past decades, a group of small non-coding RNAs, known as micrornas (mirs) have emerged as key players in the control of cellular functions through their targeted post-transcriptional regulation of messenger RNAs (i.e., gene transcripts) in the cytoplasm. This regulatory function of mirs is pertinent to mature red cells and platelets as these cells are devoid of a nucleus and lost their transcriptional regulation mechanisms; they must depend on the available cytoplasmic post-transcriptional regulatory mechanisms for their survival, especially during their ex-vivo storage, which is linked to their quality. Therefore study of mirs in stored blood cells is an important area to enhance their quality in storage and extending their shelf-life. C D Atreya is the Associate Director for Research, Office of Blood Research and Review, Center for Biologics Research and Review at the U.S. Food and Drug Administration, USA. He has more than 70 scientific publications in peer-reviewed journals and also serves on the Editorial Board for scientific journals of repute in his field of expertise. Chintamani.Atreya@fda.hhs.gov Page 22

3 Ken Mills, 2016, 7:4 (Suppl) Ken Mills Queen s University Belfast, UK Molecular basis of acute myeloid leukemia The advancement of next generation sequencing has identified a spectrum of mutations that contribute to the different types of blood cancers. These mutations can be used for the diagnostic classification and monitoring but in acute myeloid leukemia (AML) and with the exception of acute promyelocytic leukemia (APL); have not resulted in the development of novel targeted therapies. In this keynote presentation, the author will explore the range of mutations and their interactions, examine some of the molecular consequences of these and potentially how the epigenetic therapies may be useful across the different sub-types. Ken Mills is the Chair of Experimental Hematology in the Centre for Cancer Research and Cell Biology (CCRCB) in Queen s University Belfast, UK. He coordinates the activities of the Blood Cancer Research Group with a focus on the molecular aspects of MDS and AML to identify novel therapies. He has published over 135 papers, several book chapters and he is on several Editorial Board and a regular Reviewer for high impact journals and national and international funding bodies. k.mills@qub.ac.uk Page 23

4 J J Michiels, 2016, 7:4 (Suppl) J J Michiels Goodheart Institute, Netherlands 2016 WHO clinical molecular and pathological criteria for classification and staging of myeloproliferative neoplasms (MPN) caused by MPN driver mutations in the JAK2, MPL and CALR genes in the context of new 2016 WHO classification: Prognostic and therapeutic implications The 2016 WHO-CMP classification proposal defines a broad spectrum of JAK2 V617F mutated MPN phenotypes: Normocellular ET, hypercellular ET due to increased erythropoiesis (prodromal PV), hypercellular ET with megakaryocytic-granulocytic myeloproliferation and splenomegaly (EMGM or masked PV), erythrocythemic PV, early and overt classical PV, advanced PV with MF and post-pv MF. ET heterozygous for the JAK2 V617F mutation is associated with low JAK2 mutation load and normal life expectance. PV patients are hetero-homozygous versus homozygous for the JAK2 V617F mutation in their early versus advanced stages with increasing JAK2 mutation load from less than 50% to 100% and increase of MPN disease burden during lifelong follow-up in terms of symptomatic splenomegaly, constitutional symptoms, bone marrow hypercellularity and secondary MF. Pretreatment bone marrow biopsy in prefibrotic MPNs is of diagnostic and prognostic importance. JAK2 exon 12 mutated MPN is a distinct benign early stage PV. CALR mutated hypercellular thrombocythemia show distinct PMGM bone marrow characteristics of clustered larged immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are not seen in JAK2 mutated ET and PV. MPL mutated normocellular thrombocythemia is featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei without features of PV in blood and bone marrow. Myeloproliferative disease burden in each of the JAK2, CALR and MPL MPNs is best reflected by the degree of anemia, splenomegaly, mutation allele burden, bone marrow cellularity and myelofibrosis. J J Michiels is the founder of the Goodheart Institute & Foundation. He served as Assistant Professor to Professor of Nature Medicine at A. Kr. von dem Borne Department of Hematology, as a Consultant Scientist at Academic Medical Center Amsterdam during , as Consultant professor Hematology at Medical Diagnostic Center, Rijnmond Rotterdam He is the Co-founder of Central European Vascular Forum: CEVF 2003 at University Hospital Antwerp, Belgium, Co-founder of European Society of Vascular Medicine: ESVM. He is also a founder of European Working Group on Myeloproliferatieve Disorders: EWG. MPD during and European Working Group on Myeloproliferative Neoplasms: EWG.MPN. His research interests reflect in his wide range of publications in various national and international journals. He serves as a member of various associations apart from being Editorial board member of many reputed journals. goodheartcenter@upcmail.nl Page 24

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6 John Batchelor, 2016, 7:4 (Suppl) John Batchelor Central Manchester Foundation Trust, UK Coagulopathy in traumatic brain injury: Current concepts and controversies Coagulopathy following traumatic brain injury (TBI) is a well recognized pathophysiological state following head injury. A meta-analysis by Epstein et al (2014) found that the weighted average number of patients with coagulopathy following traumatic brain injury was 35.2%. The temporal pattern of coagulopathy is viable. Some patients have an early transient raise in coagulation parameters others have more delayed response. The most important coagulation parameter is currently an area of debate. Some others suggest that the PT is the most important predictor of hemorrhagic progression. Other authors suggest that thrombocytopenia is the most important predictor of hematoma progression. The presence of traumatic brain induced coaguopathy increases the risk of hematoma progression by an odds ratio of The aim of this talk is to review the characteristics of this disease process and to discuss possible etiological mechanisms responsible for this response. John Batchelor is a Consultant in Emergency Medicine at Central Manchester Foundation Trust, UK. He is also an Honorary Lecturer at Manchester Metropolitan University. He was graduated from Leeds University England in He is a Fellow of the Royal College of Surgeons of Ireland and Fellow of the Faculty of Emergency Medicine of England. He undertook his MD thesis at University College London. His current research interest lies in the area of risk factors for intracranial hemorrhage in both adults and pediatrics secondary to coagulopthy and thrombocytopenia. johnbatchelor@msn.com Page 44

7 Rajavashisth Tripathi, 2016, 7:4 (Suppl) Rajavashisth Tripathi Banaras Hindu University, India Shotha and the unified theory of inflammatory diseases Shotha is a term that was used in Charaka Samhita ( BCE) to explain the inflammatory immune response to either internal causes within the body due to endogenous factors or external causes such as infection and injury due to exogenous factors. Resolution of shotha or inflammation critically contributes to the maintenance of human health by overcoming adverse conditions presented throughout life including communicable and non-communicable diseases. Blood cells (among them mononuclear phagocytes, T cells, B cells, natural killer cells and mast cells), all thought to originate from circulating hematopoietic and immune precursors and key resident cells of the tissues orchestrate aspects of the acute and chronic shotha that underlie diseases of many organs. Inflammatory diseases are accompanied by a coordinated series of common mechanisms that is initiated by expression of cytokines, growth factors, mitogens and morphogens leading to a disturbance in homeostatic balance causing oxidative stress, tissue injury, extracellular matrix remodeling, angiogenesis and fibrosis in diverse target tissues. Careful resolution of shotha formed one of the central themes in treating pathological conditions through drugs, diet or life style modifications in Ayurvedic System of Medicine which emphasized precautions not to overwhelm and aggravate the immune system more than what is needed. Our recent studies on the regulation of macrophage-mediated inflammation by food substances and Ayurvedic rasayanas strongly suggest the involvement of pro and anti- inflammatory macrophages in maintaining homeostatic balance. Results of these studies strongly favor the conclusion that shotha or inflammation may contribute to a number of degenerative conditions in modern humans. Rajavashisth Tripathi is an internationally renowned Scientist with Professor of Medicine appointments at the David Geffen School of Medicine at UCLA and at the Charles R. Drew University of Medicine and Science in Los Angeles. His research work is focused on molecular mechanisms underlying the pathogenesis of modern diseases strongly linked to inflammation. He has extensive experience as Director of research laboratories and related administration by implementing research programs funded by National Institute of Health, American Heart Association, Eisner Foundation, Phillip Morris External Research Program and the Department of Biotechnology, Government of India. Currently, he has taken a Visiting Professorship at the Banaras Hindu University in India to study molecular and Ayurvedic biology of inflammation. rajavashisth@ucla.edu Page 45