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Loss-of-Function Mutations in Dnmt3a and Tet2 Lead to Accelerated Atherosclerosis and Convergent Macrophage Phenotypes in Mice
http://www.bloodjournal.org/content/132/Suppl_1/745

Nov 20th, 2018 - Clonal hematopoiesis of indeterminate potential (CHIP) was recently identified as a major risk factor for development of both hematologic malignancies and atherosclerotic cardiovascular disease in humans. The most commonly mutated gene in CHIP, DNMT3A, is a de novo DNA methyltransferase. The second most commonly mutated gene is TET2, an enzyme which can lead to loss of DNA methylation, and thus...

Elevated Von Willebrand Factor May Abrogate Bleeding Phenotype in a Male with a Non-Null F8 Mutation
http://www.bloodjournal.org/content/132/Suppl_1/3787

Nov 20th, 2018 - Introduction: Although FVIII activity (FVIII:C) correlates with phenotype in most Hemophilia A males, some have bleeding phenotypes milder than predicted by FVIII:C. Analysis of these individuals may provide additional insight into the relationship between F8 genotype and bleeding phenotype, identify additional factors that modulate FVIII, refine the classification of Hemophilia A and improve c...

Altered Epigenetic Maturation in Early Erythroid Cells from Diamond Blackfan Anemia Patients Treated with Transfusions, Corticosteroids, or in Remission
http://www.bloodjournal.org/content/132/Suppl_1/752

Nov 20th, 2018 - Background: Diamond Blackfan anemia (DBA) is a congenital anemia characterized by failure of adequate erythrocyte expansion from hematopoietic precursors. The genetic basis of DBA is largely established, with mutation or deletion of at least 19 structural ribosomal protein (RP) genes, a RP chaperone (TSR2), or a pivotal erythroid transcription factor (GATA1) identifiable in most DBA cases. Howe...

Non Invasive Evaluation of Hepatic Iron Concentration By Fibroscan in Transfusion-Dependent Egyptian Patients with Chronic Hemolytic Anemia
http://www.bloodjournal.org/content/132/Suppl_1/1061

Nov 20th, 2018 - Background: Transient elastography (Fibroscan®) is an ultrasound technique used to measure liver stiffness (LS), and thus assess for liver fibrosis, in patients with various chronic hepatic disorders. It can also be used to predict severity in multiple other diseases that might affect LS such as amyloidosis and possibly conditions associated with iron overload. Objectives: To assess the frequen...

Proliferative Sickle Cell Retinopathy in SS and SC Hemoglobinopathies: Identification of New Candidate Genes
http://www.bloodjournal.org/content/132/Suppl_1/2368

Nov 20th, 2018 - Retinopathy is one of the major clinical manifestations of sickle cell disease. Its clinical aspects vary depending on the presence or absence of vaso-proliferation, classifying this complication as non-proliferative and proliferative sickle cell retinopathy (PSCR). Endothelial cell activation, injury and dysfunction are importantly involved with pathophysiological mechanisms of sickle cell dis...

Impact of Cumulative Dose of Carfilzomib in Combination with Lenalidomide and Desamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real Life Survey of the Sicilian Myeloma Network
http://www.bloodjournal.org/content/132/Suppl_1/5636

Nov 20th, 2018 - Background: Triplet-based lenalidomide plus dexamethasone (Rd) combinations have become the new standard of care for early relapse and refractory multiple myeloma (RRMM). Carfilzomib is a novel selective proteasome inhibitor (PI) with high efficacy in RRMM. The ASPIRE phase 3 trial showed the superiority of carfilzomib-based triplet (KRd compared to Rd), leading to approval of K for RRMM. Howev...

Non-Effectiveness of Using RICE Post RDHAP or RDHAP Post RICE after Failure of First Line Salvage Therapy in DLBCL Patients Who Are Eligible for ASCT
http://www.bloodjournal.org/content/132/Suppl_1/4226

Nov 20th, 2018 - Background: The treatment of relapsed or refractory diffuse large B cell lymphoma (DLBCL) remains challenging. The use of salvage chemotherapy followed by autologous stem cell transplantation (ASCT) in young and fit patients is considered the standard of care. RDHAP (rituximab, dexamethasone, high dose cytosine arabinoside and cisplatin) and RICE (rituximab, ifosfamide, carboplatin, and etoposi...

TBK1/Ikkε Inhibitor Amlx Blocks Multiple Myeloma Cell Growth in Vitro and In Vivo
http://www.bloodjournal.org/content/132/Suppl_1/4504

Nov 20th, 2018 - Multiple myeloma (MM) is the most frequent cancer to involve the skeleton and remains incurable for most patients, thus novel therapies are needed. MM bone disease is characterized by osteolytic lesions that contribute significantly to patient morbidity and mortality. We showed that TBK1 signaling is a novel pathway that increases osteoclast (OCL) formation in Paget's disease, an inflammatory b...

Mean Platelet Volume Predicts Mortality in Sickle Cell Disease
http://www.bloodjournal.org/content/132/Suppl_1/2383

Nov 20th, 2018 - Background: Sickle cell disease (SCD) is a life-threatening disease with varied clinical spectrum and severity leading to premature death. There is a lack of validated prognostic markers in SCD. Recent evidence suggests that inflammation and platelet adhesion plays a critical role in the pathophysiology of vaso-occlusion in SCD. Elevated Mean Platelet Volume (MPV) values are associated with a h...

GATA/Heme Multi-Omics Reveals a Trace Metal-Dependent Erythrocyte Developmental Mechanism
http://www.bloodjournal.org/content/132/Suppl_1/500

Nov 20th, 2018 - By functioning as an enzyme cofactor, hemoglobin component and gene regulator, heme is vital for life. One mode of heme-regulated transcription involves amplifying the activity of GATA-1, a key determinant of erythrocyte differentiation. To discover biological consequences of the metal cofactor-transcription factor mechanism, we used CRISPR/Cas9 to delete intron 1 and 8 GATA motifs in Alas2, en...

Notch Activation Rescues Exhaustion in CISH-Deleted Human iPSC-Derived Natural Killer Cells to Promote In Vivo Persistence and Enhance Anti-Tumor Activity
http://www.bloodjournal.org/content/132/Suppl_1/1279

Nov 20th, 2018 - Cytokine-inducible SH2-containing protein (CIS) is a critical negative regulator of IL-15 signaling in natural killer (NK) cells and is encoded by CISH gene in human. Recent studies in a murine model demonstrate that CIS is a potent inhibitory checkpoint in NK cell-mediated tumor immunity. However, it is unclear if CIS similarly regulates human NK cell-mediated anti-tumor activity. Unlike CTLA-...

Impact of CD34 Cell Dose Infused on the Duration of Absolute Neutropenia after High Dose Melphalan and Autologous HCT for Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/2156

Nov 20th, 2018 - Background: High-dose melphalan with autologous stem cell transplantation (AHCT) is a key component in the treatment of patients with multiple myeloma (MM). The use of AHCT has been shown in several clinical trials to improve event-free and overall survival and is accepted as standard of care in medically fit patients. The use of high doses of melphalan is associated with a period of myelosuppr...

T Cell Metabolism and Memory
http://www.bloodjournal.org/content/132/Suppl_1/SCI-6

Nov 20th, 2018 - Lymphocyte activation leads to rapid proliferation and differentiation and we have shown that CD4 T cell subsets are metabolically distinct. These specific metabolic programs may allow new understanding and approaches to manipulate immunity. Using metabolic network analysis of metabolomics and proteomics we defined several metabolic nodes differentially utilized by CD4 T cell subsets, including...

Clinical Relevance of Diagnostic Criteria for Hemophagocytic Lymphohistiocytosis (HLH) and Survival Outcome of Adult HLH Patients: A Single-Center Prospective Cohort Study
http://www.bloodjournal.org/content/132/Suppl_1/3718

Nov 20th, 2018 - Introduction Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated life-threatening condition in which activated macrophages phagocytize hematopoietic cells in various clinical situations from physiologic reactions to pathologic conditions such as malignancy. The diagnosis of HLH is currently done according to the HLH-2004 criteria which were mainly based on pediatric experiences even ...

Generation of an Immortalized Erythroid Progenitor Cell Line Directly from Peripheral Blood Mononuclear Cells without Using Mobilized CD34+ Cells
http://www.bloodjournal.org/content/132/Suppl_1/1032

Nov 20th, 2018 - A reliable stable human erythroid progenitor cell line that can differentiate to the later stages of erythropoiesis is an important cellular model for studying molecular mechanisms of human erythropoiesis in physiological and pathological situations. An erythroid progenitor cell line (HUDEP) was derived from cord blood haematopoietic stem cells (HSCs) by doxycycline inducible expression of HPV ...

Development of an Algorithm to Predict Mortality in Patients with Sepsis and Coagulopathy
http://www.bloodjournal.org/content/132/Suppl_1/3791

Nov 20th, 2018 - Introduction: Sepsis is a systemic response to infection which results in a high rate of mortality worldwide. The pathophysiology of sepsis is complex; although sepsis is often defined on the basis of the overwhelming host inflammatory response, this disease process also involves infection response, hemostatic dysregulation, endothelial dysfunction, and platelet activation. Improved ability to ...

Identification of Gene Regulatory Networks Governing Stemness Properties of Human HSC and LSC
http://www.bloodjournal.org/content/132/Suppl_1/3832

Nov 20th, 2018 - The gene regulatory networks (GRN) governing maintenance and expansion of normal and leukemic human hematopoietic stem-cells (HSC and LSC) are not well understood. Typically, GRNs are inferred from gene expression (GE) data of a limited subset of pre-selected genes implicated to be relevant to the cell types being studied. Such data are commonly derived from relatively homogeneous cell populati...

Clinical Spectrum of Patients with Pathogenic Variant of STAT3 conferring Gain-of-Function: A Mimic of Autoimmune Lymphoproliferative Syndrome
http://www.bloodjournal.org/content/132/Suppl_1/3723

Nov 20th, 2018 - Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder caused by defective fas-mediated apoptosis. Patients often present in childhood with lymphoproliferation, splenomegaly and multilineage cytopenias (Price et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood 2014). Though mutations in the FAS gene account for the major...

Proteome Analyses and Single-Cell RNA Sequencing Reveal Age-Dependent Re-Wiring of Central Carbon Metabolism in Myeloid-Biased Subsets of Human Hematopoietic Stem Cells
http://www.bloodjournal.org/content/132/Suppl_1/873

Nov 20th, 2018 - Background: Diminishing potential to replace damaged tissues is a hallmark for aging of somatic stem cells, but the mechanisms leading to aging remain elusive. Applying comprehensive proteomics studies on human hematopoietic stem and progenitor cells (HPCs) as well as 5 other cell populations that constitute the bone marrow niche, we have acquired a systems understanding of the mechanisms invol...

Antithrombotic Therapy Management in Patients with Inherited Bleeding Disorders and Ischaemic Heart Disease: A Single-Center Experience
http://www.bloodjournal.org/content/132/Suppl_1/1213

Nov 20th, 2018 - Introduction: In the last decades, the life expectancy of patients with hemophilia A (HA), hemophilia B (HB) and von Willebrand disease (VWD) has substantially improved. As a result, these patients experience age-related comorbidities, especially ischaemic heart disease. Safety and efficacy of antiplatelet drugs in patients with inherited bleeding disorders remain unclear, while there is no evi...