Day 1 :
Keynote Forum
Robert H. Schiestl
University of California, Los Angeles, USA
Keynote: 6-thioguanine in vivo selection for hematopoietic stem cell transplantation
Time : 10:00-10:30
Biography:
Robert H. Schiestl has obtained his PhD from the University of Vienna at the age of 23 years. He was postdoctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before being professor at Harvard at the age of 31 where he stayed for 10 years. Since 15 years he is professor at UCLA with 187 publications, 10 patents and 2 startup companies.
Abstract:
Hematopoietic stem cell transplantation (HSCT) is often the only/last treatment option of some malignancies, congenital diseases and bone marrow failure. For efficient engraftment of donor HSC’s stem cell niches have to be provided. Here we developed an in vivo selection scheme for HSCT based on the fact that 6-thioguanine (6TG) toxicity is essentially predicated on its HPRT mediated conversion to thioguanine nucleotide and strongly myelosuppressive. At appropriate concentrations 6TG is strongly myeloablative with little toxicity to other tissues. Therefore it is possible to eliminate diseased bone marrow and replace it with healthy donor bone marrow that lacks HPRT.rnWe have shown that only Hprt proficient cells are susceptible to 6-TG allowing selection in favor of Hprt deficient donor HSC’s in vivo and that a 4 week selection regimen results in a 95% replacement of the hosts marrow. Engraftment is more robust with 6-TG selection than with radiation. The proposed method offers selection through a less toxic compound (compared to other schemes) hence less side effects, use of smaller, siRNA-producing vectors (therefore potentially more efficient), possible use of non-integrating vectors and less patient discomfort.rnThe general aim of this project is to show that HSC’s deficient for HPRT can be selected for in vivo through 6TG administration, that this procedure would be applicable for conditions like hematological malignancies, congenital diseases and bone marrow failure i.e. where HSCT is indicated and to test all aspects of this procedure to eventually allow for phase I clinical trials.rn
Keynote Forum
C Cameron Yin
The University of Texas, USA
Keynote: Immunoglobulin is expressed in acute myeloid leukemia and affects myeloblasts survival
Time : 10:30-11:00
Biography:
C Cameron Yin has received her MD from Beijing Medical University and her PhD from the University of Wisconsin-Madison. She is currently an Associate Professor in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center. In addition to clinical responsibilities on the Leukemia, Lymphoma and Molecular Diagnostic services, she has been actively participating in multiple research projects in the molecular genetic abnormalities in leukemia and lymphoma, which has led to over 100 research papers and over 20 book chapters.
Abstract:
We studied immunoglobulin gamma heavy chain (IgG) expression in acute myeloid leukemia (AML) and found that IgG was expressed at a high frequency and level in AML cell lines and primary myeloblasts but not in monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. We further detected IgG VHDJH transcripts in AML cell lines and sorted primary myeloblasts, confirming that IgG expression was indeed produced by AML cells. AML-IgG gene rearrangements showed evidence of somatic hyper mutation and restricted (AML cell lines) or biased (primary myeloblasts) V usage. Anti-human IgG reduced cell viability and induced apoptosis in AML cell lines. Our findings suggest that AML-IgG may play a role in leukemogenesis and AML progression. AML-IgG may serve as a useful molecular marker for monitoring minimal residual disease or designing target therapy.
- Hematologic Malignancies
Location: 1
Chair
Ken Mills
Queens University Belfast, UK
Co-Chair
Ulla Randen
Oslo University Hospital, Norway
Session Introduction
Michael Keng
University of Virginia, USA
Title: The current landscape of myelodysplastic syndromes
Biography:
Michael Keng received his BS and MD degrees from Michigan State University in East Lansing, Michigan. He completed his Internal Medicine residency at University of Southern California in Los Angeles, California, and Hematology and Medical Oncology fellowship at the Cleveland Clinic in Cleveland, Ohio. He then joined the University of Virginia (Charlottesville, Virginia) in 2014. He currently holds a faculty appointment in Medicine in the Division of Hematology/Oncology at University of Virginia. His clinical areas of interest are focused on clinical trials in hematologic malignancies, including myelodysplastic syndromes, leukemias, and other myeloid malignancies and bone marrow failures. He has a special interest in treating the elderly population, determining optimal combinations and timing of targeted agents, and studying patient safety and quality improvement
Abstract:
Myelodysplastic syndromes (MDS) are a heterogeneousgroup of clonal hematopoietic stem cell disorders characterized by cytopenias as a result of ineffective hematopoiesis and a propensity to progress to acute myeloid leukemia and premature mortality in many patients. MDS, especially lower-risk MDS, can be diagnostically challenging with substantial morphologic overlap with nutritional deficiencies, toxic injury, infections, and some inherited disorders. Recent studies have identified novel genetic changes, which help to provide a better understanding of the underlying pathobiology of MDS. This session will review how to distinguish lower-risk from higher-risk MDS, goals of therapy, and standard, non-transplant treatment approaches. The session will then build on these basics to highlight mechanistic-based approaches justifying novel monotherapies and combinations of drugs to treat lower-risk and higher-risk disease.
Ken Mills
Queen’s University Belfast, UK
Title: Identifying novel epigenetically induced synthetic lethality therapeutic combinations for high risk MDS/AML
Biography:
Ken Mills is Chair of Experimental Haematology in the Centre for Cancer Research and Cell Biology (CCRCB) in Queen’s University Belfast. 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 is on several editorial board and a regular reviewer for high impact journals and national and international funding bodies.
Abstract:
High risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of the aging; with many patients are unable to tolerate intensive therapies and an unmet need for novel therapeutic approaches. Epigenetic silencing of genes in MDS and AML can occur via the recruitment of histone deacetylases (HDACs) or by aberrant DNA hyper-methylation; these changes can be reversed making them prime targets for therapy. The development of agents that inhibit HDACs (HDACi) or the DNA methyl transferase activity (DNMTi) have proven successful in certain malignancies and have shown promise of increasing treatment tolerability. However, it is an over-simplification to assume that epigenetic based therapies simply allow the expression of tumor suppressor genes; so a greater understanding of their mode of action is required to develop more rationale combinations. Integrative analyses involving transcriptomics with methylation profiling or ChIP-seq of chromatin associated with histone acetylation modification marks has been undertaken to identify epigenetic primed induced synthetic lethal therapeutic combinations. The integrated analysis has identified novel primed gene and network targets specifically activated as a response to the epigenetic therapies. These studies not only provide further insight into the molecular mode of action of the epigenetic therapies but have identified agents that might work synergistically in combination thus providing potential novel therapies for MDS / AML patients.
Biography:
Robert H Schiestl has obtained his PhD from the University of Vienna at the age of 23 years. He was Postdoctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before being Professor at Harvard at the age of 31 where he stayed for 10 years. Since 15 years he is Professor at UCLA with 187 publications, 10 patents and 2 startup companies.
Abstract:
Intestinal microbiota plays a role in the nutrient metabolism, modulation of the immune system, arthritis, obesity and intestinal inflammation. In the literature there have been huge differences in the same Atm deficient mice in different labs reported. When our lab moved from Harvard to UCLA we found a similar difference in genetic instability and logevity. When we changed the intestinal microbiota back to conventional microbiota we could reproduce the phenotype at Harvard. We tested Atm deficient mice for genotoxicity, genetic instability, DNA damage, inflammation markers, cancer latency and longevity and high throughput sequencing of the intestinal microbiota. Isogenic mice from different housing facilities showed a four fold difference in life expectancy, a 4.5 fold difference in genetic instability and DNA damage. The onset of lymphomas was significantly 2 fold different. We sequenced the microbiota of both facilities and found Lactobacillus johnsonii 456 as dominant bacterial strain in the health beneficial microbiota. Just this bacterium by itself reduced genotoxicity, reduced inflammation and reduced levels of cytotoxic T cells in the liver and blood. We also found similar differences in Trp53 deficient and even in wildtype mice. The underlying mechanisms are probably due to inflammation promotion or suppression mediated by the intestinal microbiota. The understanding of this effect may lead to a breakthrough in the understanding of the causes of carcinogenesis, which might lead to prevention of AT, a currently incurable progressive disease and possibly other cancer-prone DNA repair deficient diseases or even wildtype mice and people.
Ulla Randen
Oslo University Hospital, Norway
Title: Primary cold agglutinin disease (CAD) associated lymphoproliferative disease: a new entity
Biography:
Ulla Randen is a consultant pathologist at Oslo University Hospital with a speciality in hematopathology, including flow cytometry. She has performed research on different small B-cell lymphoproliferative diseases with a special interest in patients with chronic cold agglutinin disease (CAD).
Abstract:
Primary chronic cold agglutinin disease (CAD) is a rare hemolytic disease (1:1.000.000) mediated by monoclonal IGHV4-34-encoded cold agglutinins with a predominant specificity for the blood group antigen I. These patients have previously been given a variety of diagnoses on bone marrow biopsies, from ‘no signs of lymphoid infiltration’ to an overt lymphoma, most often lymphoplasmacytic lymphoma (Mb. Waldenström). However, studies including flow cytometry have shown that >90% of them, if not all, have a monoclonal B-cell proliferation. We have therefore performed studies on a larger group of CAD patients and examined bone marrow aspirates and biopsies to better type the underlying lymphoproliferative disorder. Bone marrow biopsies typically showed small infiltrates (median infiltration: 10% of marrow cells) with a mature B- cell immunophenotype. Morphologically, the infiltration did not fit with lymphoplasmacytic lymphoma, as neither mast cells or plasmacytoid cells were present, nor did the small B cells express plasma cell differentiation-associated markers. A limited number of mature monoclonal IgM+ plasma cells were present outside the lymphoid nodules and were diffusely scattered throughout the marrow and regarded as part of the lymphoproliferative disease, as these produce the monoclonal anti-I antibodies. Of interest, the MYD88 L265P mutation, typical of lymphoplasmacytic lymphoma, was not detected. We conclude that cold agglutinin-associated lymphoproliferative disease displays homogeneous histological and immunophenotypic features that distinguishes this entity from lymphoplasmacytic lymphoma, and thereby distinguishes chronic cold agglutinin disease from Mb. Waldenström.
Katarzyna Piwocka
Nencki Institute of Experimental Biology, Poland
Title: The therapeutic potential of the translation initiation factor eIF2α serine 51 phosphorylation for chronic myeloid leukemia
Biography:
Katarzyna Piwocka has obtained her MSc degree in Microbiology from the Warsaw University in 1994 and PhD in Biology, specialization Biochemistry from the Nencki Institute in Warsaw, Poland in 2001. She has received Postdoctoral Training at the Bio-Sciences Institute, University College Cork, Ireland (2003-2004). In 2014, she has received Habilitation in Biological Sciences. Currently, she is an Associate Professor, Head of the Department of Biochemistry (since 2015) and Head of the Laboratory of Cytometry (since 2010) at the Nencki Institute in Warsaw, Poland. She has won several awards including a five-year ISAC Scholar fellowship from the International Society for Advancement for Cytometry
Abstract:
The t (9; 22) chromosomal translocation present in almost all CML patients’ results in the expression of a 210 kDa fusion protein known as Bcr-Abl. Bcr-Abl is a tyrosine kinase with potent oncogenic properties, which is the underlying cause of CML. Although Bcr-Abl has been an attractive target for therapeutic intervention, CML patients frequently develop resistance to pharmacological inhibitors of Bcr-Abl. Therefore, the identification of intracellular pathways that contribute to the oncogenic effects of Bcr-Abl and development of drug resistance has been an important goal of CML research. As a result of an international collaboration between Poland and Canada, we have identified a novel pathway of Bcr-Abl signaling, which is the phosphorylation of α subunit of the translation initiation factor eIF2 at serine 51 (eIF2αS51P). The eIF2αS51P is a master regulator of stress and an important mechanism utilized by cells to adapt to various forms of environmental stress through the translational control of select mRNAs that can promote either cell survival or death. We found that Bcr-Abl induces eIF2αS51P in CML cells in culture, CML patients and mouse xenograft tumor assays via the activation of the endoplasmic-reticulum (ER)-resident kinase PERK. Genetic inactivation of eIF2αS51P impairs the oncogenic properties of Bcr-Abl and increases the sensitivity of CML cells to the anti-tumor drug imatinib in culture and mice. Our work demonstrates that pharmacological inhibition of eIF2αS51P is likely to be a suitable approach to increase the sensitivity of anti-tumor drugs targeting Bcr-Abl as a means to combat CML disease.
Biography:
Abdel Rahim Mahmoud Muddathir has completed his PhD at the age of 32 years from Alzaiem Alazhari University and did his PhD practical work in CMM at Karolinska Institute (Sweden). He had the fellowship of IBMS and also is Sudan advisory board member of ASCP. He is Editorial board member of Austin Journal of Cancer and Clinical Research and he was the dean of Medical Laboratory Sciences School in Sharq Elniel College.
Abstract:
Objectives: In Sudan, CML is the most common cancer among males and the second most common cancer among females our study aimed to determine the frequencies of BCR-ABL transcript variants studied in Sudanese patients with chronic myeloid leukemia (CML). Methods: This is a descriptive cross-sectional study carried out in 112 CML patients who attended at different clinics of Khartoum state, Sudan from February 2007 to December 2010. Transcript analysis was successful in 109 venous blood and bone marrow samples using quantitative real-time-polymerase chain reaction (RT-PCR). Results: The transcripts analysis of 109 patients showed that 32.1% (35/109) expressed one or both of the P210 BCR/ABL rearrangements (b2a2 andb3a2). Of those 35 (32.1%), 21 patients expressed b2a2, 6 expressed b3a2, and 8 expressed both transcripts b2a2/b3a2. The remaining 74 patients revealed transcripts combination of P190 BCR/ABL and P210 BCR/ABL (e1a2/b2a2/b3a2), of which 19 patients had all the transcripts (e1a2/b2a2/b3a2), 33 revealed 2 transcripts (e1a2/b2a2), and the remaining 22 patients had (e1a2/b3a2).
Biography:
C Cameron Yin has received her MD from Beijing Medical University and her PhD from the University of Wisconsin-Madison. She is currently an Associate Professor in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center. In addition to clinical responsibilities on the Leukemia, Lymphoma and Molecular Diagnostic services, she has been actively participating in multiple research projects in the molecular genetic abnormalities in leukemia and lymphoma, which has led to over 100 research papers and over 20 book chapters.
Abstract:
CD5-posiitve B-cell lymphomas are a heterogenous group of neoplasms. Classification of this group of lymphomas has important clinical and prognostic significance. CD5-positive B-cell lymphomas consist primarily of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). However, CD5 expression has been reported in a number of other B-cell lymphomas. We report the clinical, morphologic, immunophenotypic and molecular genetic features of several series of CD5-positive B-cell lymphomas that lack the prototypic characters of CLL/SLL or MCL, including follicular lymphoma, MALT lymphoma, nodal marginal zone lymphoma and lymphoplasmacytic lymphoma. Our results show that CD5 expression is often associated with an increased tendency of disseminated disease in MALT lymphoma and nodal marginal zone lymphoma, but these patients usually have an indolent clinical course and excellent overall survival with appropriate management. However, in follicular lymphoma, CD5 expression is associated with a higher International Prognostic Index, higher rate of transformation to diffuse large B-cell lymphoma, and shorter progression-free survival. We summarize that CD5 expression not only produces diagnostic challenges in the classification of CD5-positive B-cell lymphomas, but also bears prognostic significance.
- Special session
Session Introduction
Jay S Raval
University of North Carolina, USA
Title: Acquired thrombotic thrombocytopenic purpura: Disease pathogenesis, laboratory monitoring and current treatment strategies
Biography:
Jay S Raval has received his Undergraduate and Medical degrees from the University of North Carolina at Chapel Hill, during which he was a Howard Holderness Distinguished Medical Research Scholar. He was trained at the University of Pittsburgh where he has completed a Surgical Internship followed by Residency Training in Clinical Pathology. He went on to complete Blood Banking/Transfusion Medicine Fellowship Training in the joint program between the University of Pittsburgh and The Institute for Transfusion Medicine, where he has developed an interest in therapeutic apheresis and hematopoietic progenitor stem cell collection and processing. He stayed as Faculty at University of Pittsburgh and The Institute for Transfusion Medicine before joining the University of North Carolina at Chapel Hill, where he is the Medical Director of Therapeutic Apheresis, Associate Medical Director of Transfusion Medicine Services and Associate Medical Director of the Hematopoietic Progenitor Cell Laboratory. He has published over 50 peer reviewed articles, authored 8 book chapters and is on the Editorial Board of 7 journals. His research interests include: Thrombotic thrombocytopenic purpura; red blood cell storage lesion; evidence-based therapeutic apheresis and transfusion medicine practices; hematopoietic progenitor stem cell collection and processing and pathology education
Abstract:
that is due to platelet-von Willebrand Factor microthrombi in the circulation. The discovery of ADAMTS13, its role in cleaving unusually-large von Willebrand Factor multimers, and the detection of autoantibodies/inhibitors directed against this essential enzyme have reinforced the important roles of plasma exchange and immunosuppression in patients with this critical illness. TTP disease pathogenesis, routine and novel laboratory markers for diagnosing and following patients with TTP, and up-to-date treatment strategies will be covered in this lecture.
- Track2: Blood- Components and Functions
Track3: Hemato-immunology & Stem Cell Research
Location: 2
Chair
Dianzheng Zhang
Philadelphia College of Osteopathic Medicine, USA
Co-Chair
Jay S. Raval
University of North Carolina, USA
Session Introduction
Dianzheng Zhang
Philadelphia College of Osteopathic Medicine, USA
Title: MicroRNA as biomarker for acute graft versus host disease
Biography:
Dianzheng Zhang has completed his PhD from University of Arizona and Postdoctoral studies from Baylor College of Medicine. He assumed an Assistant Professor position at PCOM in 2006 and promoted to an Associate Professor in 2011. He has published more than 40 papers in reputed journals and has served as a chairman for multiple international conferences.
Abstract:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft-versus-host disease (aGVHD) is a major complication in up to 75% of allo-HSCT. It is known that donor-derived T lymphocytes are the primary effector cells responsible for triggering aGVHD and mechanistically an enhanced Th1 response is considered the leading cause of aGVHD. However, the exact mechanisms involved in aGVHD development remain largely unknown. The lack of a reliable predicative biomarker of aGVHD onset prevents preemptive treatment and impedes widespread and successful application of this therapy. By monitor the changes of the miRNA levels after transplant, we found that the levels of miR-181a were reduced significantly 3-4 days prior to the onset of aGVHD. Importantly, the degree of its reduction correlated with the severity of aGVHD. Mechanistically, miR-181a affects the function of T lymphocytes by down-regulating IFN-γ in a dose-dependent manner. In addition, using a murine allo-HSCT model, we demonstrated that murine miR-181b, the human miR-181a homolog, served as an effective predictor of aGVHD. Moreover, expression of this microRNA also ameliorated the severity of aGVHD. Collectively, we demonstrated that the level of miR-181a can serve as a reliable biomarker for the prediction of the aGVHD and this provided a window for treating aGVHD preemptively. Finally, results from the experiments conducted in the mouse model indicate that manipulation of miR-181a levels may be a potential strategy in prevention of aGVHD.
Abishek B Santhakumar
Central Queensland University, Australia
Title: Role of antioxidants and polyphenols in thrombosis and haemostatic function
Biography:
Abishek B Santhakumar obtained his Masters in Laboratory Medicine at RMIT University, Australia in 2010. Linking up isolated facts into comprehensive understandings to discover something is what science is described as and this cognitive process fascinated him to pursue a PhD in Haematology at Griffith University, Australia (2011-2014). His research interest is to get cogent evidence on how natural dietary antioxidants may help alleviate the risk of thrombosis and its potential as anti-platelet therapy. He has published a number of peer-reviewed journal articles, reviews and successful in research grants. He is currently an academic/researcher at CQ University, Australia doing what he loves the most.
Abstract:
Platelet hyperactivity and oxidative stress play a central role in the pathogenesis of many disorders including cardiovascular disease, thrombosis and type 2 diabetes. Natural antioxidants and polyphenols are believed to exhibit cardio-protective properties via their free radical scavenging activity. In this research, the anti-thrombotic potential of taurine, caffeine, anthocyanin polyphenol and its active metabolite hippuric acid was evaluated. It was found that taurine and caffeine, in vitro, synergistically lowered platelet aggregation and prolonged time taken for clot formation. Dietary supplementation with a novel variety of Queen Garnet plum juice (QGPJ), rich in anthocyanins, for 4 weeks reduced platelet hyperactivity/aggregation, reduced biomarkers of oxidative stress, and favorably altered coagulation parameters in normal healthy individuals. This antithrombotic activity of QGPJ was greater under an exercise-induced model of oxidative stress in healthy individuals. Hippuric acid, in vitro, also demonstrated reduction of platelet hyperactivation. Supplementation with QGPJ did not alter thrombosis specific gene expression. The results demonstrate the potential of natural antioxidants in reducing platelet hyper activation related thrombogenesis in both normal and prothrombotic conditions. Further mechanistic studies are warranted to unveil the potential of such natural compounds in complementary antiplatelet therapy.
Shigetaka Shimodaira
Shinshu University Hospital, Japan
Title: Dendritic cell-based cancer immunotherapy
Biography:
Graduated from Shinshu University School of Medicine, Japan received MD in 1990. Specialized in Hematology and Oncology at the Graduate School of Medicine of Shinshu University and received a PhD in 1997. Studied the pathogenesis of HCV in the USC, CA, from 1999 to 2001. Conducted educational and clinical activities to promote transfusion medicine in the Shinshu University Hospital since 2002. Became a Director of Advanced Center for Cell Therapy in the Shinshu University Hospital since 2011. Became a Professor of Advanced Center for Cell Therapy, Shinshu University Hospital since 2013.
Abstract:
Despite the significant recent advances in the therapeutics for cancer, it still remains extremely difficult to treat advanced cancers with organ involvement and distant metastasis. A manufacturing technology for antigen-presenting cell (APC)-based immunotherapy is being developed, with active dendritic cell (DC), the most potent APCs of the immune system, being under investigation for therapeutic vaccination against cancer for strong induction of the T cells against tumor antigens. The ex vivo technique is being developed for DC-based cancer vaccination, most of which is the preparation of autologous mature monocyte-derived DCs derived from apheresis of patients’ blood. Cancer vaccine therapies are principally attributed to the presence of tumor-associated antigens. Wilms tumor 1 (WT1), an attractive target antigen widely expressed in every cancer, sarcoma, and leukemia, has been shown to the most potent cancer-associated antigens for immunotherapy. DC vaccine loaded with HLA class I/II–restricted WT1 peptides may be potentially strong therapeutic activity against cancers. DC-based immunotherapy targeting WT1 was indicated to be safe and feasible for the management of advanced cancers including pancreas, lung, and ovary, exhibiting ‘delayed separation’ curve in some patients. The vaccination would be feasible option even for patients with malignant brain tumor and acute leukemia after hematopoietic stem cell transplantation to control minimum residual disease. In future, the blockade of immune checkpoints in combination with DC-vaccination would be promising therapeutic strategies to activate therapeutic anti-tumor immunity for advanced cancers and hematological malignancies.
Anita Nadkarni
National Institute of Immunohematology, India
Title: Effect of group of genetic markers on induction of fetal hemoglobin and disease severity in hemoglobinopathies
Biography:
Anita Nadkarni has completed her PhD in year 1995 from University of Mumbai and Postdoctoral studies from the National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Japan. She is the Deputy Director of National Institute of Immunohematology. She made outstanding contribution to the field of molecular genetics of thalassemia and other hemoglobinopathies during the past two decades. She is recipient of many national and international awards. She has published more than 110 papers in reputed journals and has been serving as an Editorial Board Member of repute
Abstract:
As higher HbF levels in patients with β thalassemia or sickle cell anemia are associated with milder phenotypes, several groups are exploring the factors that regulate the switch from fetal to adult hemoglobin and its therapeutic potential. The contributions of cis-acting elements to HbF production are critical to understand the variable clinical phenotypes of β-thalassemia and sickle cell anemia. Recently, there has been considerable progress made in defining the loci or genomic regions that may often be involved in the regulation of the switch from fetal to adult hemoglobin. In the study we enrolled 79 β thalassemia homozygous, 11 sickle cell anemia and 14 sickle-β thalassemia individuals. Fifty age and sex matched healthy individuals were enrolled as the normal control group. Our objective was to study the effect of cis-DNA haplotypes, motifs, or polymorphisms (Pre G γ globin gene haplotypes, Aγ–δ intergenic region haplotypes XmnI and (AT)x(T)y polymorphisms, β-LCR HS2 and HS3 site motifs) that may contribute to higher HbF levels and a milder clinical course. We found that a combination of T haplotype of the Aγ–δ intergenic region,TAG Pre-Gγ haplotype, presence of the XmnI polymorphism along with the (AT)9(T)5 motif constitutes a topography that co-relates with raised HbF levels which may contribute in ameliorating the disease severity.
Sayeedul Hasan Arif
Jawaharlal Nehru Medical College, India
Title: Single donor versus pooled random donor platelet concentrates: A review of literature
Biography:
Sayeedul Hasan Arif has completed his MD in pathology in the year 1991. He has joined the Department of Pathology, J. N. Medical College, AMU Aligarh (India) as Demonstrator for three years and later joined the Department as Assistant Professor in 1995, promoted to Associate Professor in 2004 and joined as Professor in 2010 and still working on same post. He is also In-charge of Blood Bank and of Central Investigation Laboratory. He was Member of Medical Education Unit in Faculty of Medicine since 2009-2014 and Fellow in Medical Education (FIME). He has also served Hospital in the capacity of DMS from 2011-2013. He has more than 30 papers to his credit in various international and national renowned journals. He is the winner of William Harvey Research Award in Hematology-2015 for his publication for Incidental detection of Hemoglobin C trait in a 7 year male child in Journal for Hematology. He is also Member of Review Committee for various national and international journals.
Abstract:
Both platelet concentrates (PC) obtained from 6-7 Buffy coat of whole blood or single donor platelets (SDP) obtained by aphaeresis are indicated to treat hemorrhage secondary to thrombocytopenia which includes Dengue, Malaria, ITP, TTP, DIC, Septicemia etc. Dengue and Malaria are very important indications in developing countries like India. It is also used to provide prophylaxis from hemorrhage in patients with bone marrow suppression. Currently platelet transfusion therapy is limited due to several reasons, including the consequences of alloimmunization in chronically transfused patients and septic reactions caused by bacterial contamination. There is lot of discussion and debate about which platelet product should be used; many transfusion medicine services favor the primary use of PC, whereas others favor SDP. This review will discuss five areas that should be considered when there is a debate between use of SDP or PC: Infectious complications, transfusion reaction rate, leuko-depletion, reduction of transfusion frequency in patients with bone marrow aplasia and alloimmunization associated with their use and prevention. Various authors believe that SDP offers main advantages over PC for most of these issues. However, taken the issue of high cost with SDP, a PC should be considered wherever possible in developing countries like India, taking into account risk benefit ratio.
Biography:
Shyama Soorambail Keshava has completed his PhD degree in 1989 from Mangalore University. He is currently serving as a Professor in Zoology in Goa University since 2006. He has published 30 papers in reputed journals and has been serving as a Reviewer for several journals of international repute.
Abstract:
The lympho-hematopoietic elements undergo rapid multiplication in humans and are also the most radiosensitive cells. Ionizing radiations target DNA and induce mutations. Radiotherapy resulting in optimum absorbed dose will help us to minimize the unwanted side effects irradiation. The present in vivo study is undertaken to know the dispersed radiation dose-response in the peripheral blood leukocytes of cancer patients in the context of partial body irradiation. The genotoxic effect of γ-radiation was studied in HNSCC patients exposed to various cumulative doses 60Co gamma rays during radiotherapy (RT). These patients (P1 to P30) were irradiated for a period of six weeks with a daily fraction of 2 Gy, consecutively for 5 days every week. The genotoxic effects of radiation in these patients were analyzed every weekend employing the chromosomal aberration, comet assay and cytokinesis block micronucleus assay. Blood of these patients collected before starting with RT (pre-therapy) served as control samples, whereas, blood collected during the week ends at weekly intervals of 1 to 6 weeks during the course of RT served as treated (10, 20, 30, 40, 50 and 60 Gy) samples. Radio-sensitivity of these patients was analyzed by employing linear regression analysis. Genetic damage observed in all patients on a weekly basis were recorded and analyzed at the individual level in comparison with their own pre-therapy baseline data, employing student’s t-test. High level (p<0.001) intra-individual variations were observed in the genotoxic response of HNSCC patients exposed to gamma irradiation (ANOVA). Results of this study indicate a dose dependent increase of cytogenetic damage in leukocytes. Thus, cytogenetic studies in peripheral lymphocytes following gamma radiotherapy of tumors may help to understand the optimum/precise dose of radiation to be employed for RT beyond which it may lead towards the induction of secondary tumors in irradiated HNSCC patients.
Biography:
Shyama Soorambail Keshava has completed his PhD degree in 1989 from Mangalore University. He is currently serving as a Professor in Zoology in Goa University since 2006. He has published 30 papers in reputed journals and has been serving as a Reviewer for several journals of international repute.
Abstract:
The lympho-hematopoietic elements undergo rapid multiplication in humans and are also the most radiosensitive cells. Ionizing radiations target DNA and induce mutations. Radiotherapy resulting in optimum absorbed dose will help us to minimize the unwanted side effects irradiation. The present in vivo study is undertaken to know the dispersed radiation dose-response in the peripheral blood leukocytes of cancer patients in the context of partial body irradiation. The genotoxic effect of γ-radiation was studied in HNSCC patients exposed to various cumulative doses 60Co gamma rays during radiotherapy (RT). These patients (P1 to P30) were irradiated for a period of six weeks with a daily fraction of 2 Gy, consecutively for 5 days every week. The genotoxic effects of radiation in these patients were analyzed every weekend employing the chromosomal aberration, comet assay and cytokinesis block micronucleus assay. Blood of these patients collected before starting with RT (pre-therapy) served as control samples, whereas, blood collected during the week ends at weekly intervals of 1 to 6 weeks during the course of RT served as treated (10, 20, 30, 40, 50 and 60 Gy) samples. Radio-sensitivity of these patients was analyzed by employing linear regression analysis. Genetic damage observed in all patients on a weekly basis were recorded and analyzed at the individual level in comparison with their own pre-therapy baseline data, employing student’s t-test. High level (p<0.001) intra-individual variations were observed in the genotoxic response of HNSCC patients exposed to gamma irradiation (ANOVA). Results of this study indicate a dose dependent increase of cytogenetic damage in leukocytes. Thus, cytogenetic studies in peripheral lymphocytes following gamma radiotherapy of tumors may help to understand the optimum/precise dose of radiation to be employed for RT beyond which it may lead towards the induction of secondary tumors in irradiated HNSCC patients.
Jummanah Jarullah
King Abdulaziz University, Saudi Arabia
Title: Glucose 6 phosphate dehydrogenase- A pharmacogenetics gene
Biography:
Jummanah Jarullah is working as a haematological researcher for past 25 years. Her main field of expertise is in molecular hemoglobinopathies. During her career, she has published many papers and is a reviewer of many journals.
Abstract:
G6PD deficiency play important role in establishing the discipline of pharmacogenetics. Personal genomic makeup is responsible for the efficacy and side effect of the drugs in different ethnic groups. G6PD has shown marked polymorphism in many populations in past and present. This makes G6PD gene a marker for the origin, migration and genetic drift. Deficiency of G6PD enzyme is a silence phenomenon. G6PD deficient individuals have sudden unwarranted haemolytic attack. Global burden for this disease is huge. Although many countries have made G6PD neonatal screening mandatory, there remain quite a few populations who are unaware of their prevalence rate. New drug may be safe for one ethnic group while unsafe for other group since G6PD deficiency variants vary from one population to the other. Fresh drugs should therefore be tested in more than one ethnic group for safety parameters, before approval. Continued Drug Monitoring after release should monitor to spot unusual drug reactions early and to allow for prompt control. Detection of G6PD variants in various populations and its effect on various drugs will be helpful in making the drug safely administered in particular ethnic group. We are beginning an era, to learn how to deal with personal preventive and prognostic health approach instead of being draconian in our approach to health.