Hematology Commons^™

Transcutaneous Electrical Nerve Stimulation (Tens) For Pain Management In Sickle Cell Disease, Sudipta Pal, Ruchita Dixit, Soe Moe, Myron A. Godinho, Adinegara B.L. Abas, Samir K. Ballas, Shanker Ram, Uduman A.M. Yousuf

Cardeza Foundation for Hematologic Research

No abstract provided.

Beyond The Transition Of Adolescents And Young Adults With Sickle Cell Disease To Adult Care: Role Of Geography., Nina Anderson, James R. Eckman, Samir K. Ballas

Cardeza Foundation for Hematologic Research

No abstract provided.

Identification Of A Functional Genetic Variant Driving Racially Dimorphic Platelet Gene Expression Of The Thrombin Receptor Regulator, Pctp., Xianguo Kong, Lukas M. Simon, Michael Holinstat, Chad A. Shaw, Paul F. Bray, Leonard C. Edelstein

Cardeza Foundation for Hematologic Research

Platelet activation in response to stimulation of the Protease Activated Receptor 4 (PAR4) receptor differs by race. One factor that contributes to this difference is the expression level of Phosphatidylcholine Transfer Protein (PCTP), a regulator of platelet PAR4 function. We have conducted an expression Quantitative Trait Locus (eQTL) analysis that identifies single nucleotide polymorphisms (SNPs) linked to the expression level of platelet genes. This analysis revealed 26 SNPs associated with the expression level of PCTP at genome-wide significance (p < 5×10(-8)). Using annotation from ENCODE and other public data we prioritised one of these SNPs, rs2912553, for functional testing. The allelic frequency of rs2912553 is racially-dimorphic, in concordance with the racially differential expression of PCTP. Reporter gene assays confirmed that the single nucleotide change caused by rs2912553 altered the transcriptional potency of the surrounding genomic locus. Electromobility shift assays, luciferase assays, and overexpression studies indicated a role for the megakaryocytic transcription factor GATA1. In summary, we have integrated multi-omic data to identify and functionalise an eQTL. This, along with the previously described relationship between PCTP and PAR4 function, allows us to characterise a genotype-phenotype relationship through the mechanism of gene expression.

The Role Of Platelet Microvesicles In Intercellular Communication., Leonard C. Edelstein

Cardeza Foundation for Hematologic Research

In recent years, there has been exponential growth in the interest in microvesicles, which is reflected by the number of publications. Initially referred to as "platelet dust" by Peter Wolf in 1967, platelet microvesicles (PMV) are now recognized as important mediators of intercellular communication. There are examples of PMV exerting physiological effects on almost all hematological and vascular cell types, including monocytes, macrophages, neutrophils, T-cells, endothelium cells, and smooth muscle cells (SMCs). PMV can exert these effects by multiple methods: extracellular signaling through receptors, transfer of surface molecules, and delivery of intracellular contents including miRNA. Recent work suggests a complex …

Pharmacological Interventions For Painful Sickle Cell Vaso-Occlusive Crises In Adults, Tess E. Cooper, Ian R. Hambleton, Samir K. Ballas, Philip J. Wiffen

Cardeza Foundation for Hematologic Research

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the analgesic efficacy, and adverse events, of pharmacological interventions used to treat acute painful sickle cell vaso-occlusive crises in adults, aged 18 and over, in any setting.

Treatment Of Dental Complications In Sickle Cell Disease., Priti Mulimani, Samir K. Ballas, Adinegara B L Abas, Laxminarayan Karanth

Cardeza Foundation for Hematologic Research

BACKGROUND: Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in …

A Case-Control Genome-Wide Association Study Identifies Genetic Modifiers Of Fetal Hemoglobin In Sickle Cell Disease., Li Liu, Alexander Pertsemlidis, Liang-Hao Ding, Michael D Story, Martin H Steinberg, Paola Sebastiani, Carolyn Hoppe, Samir K. Ballas, Betty S Pace

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is a group of inherited blood disorders that have in common a mutation in the sixth codon of the β-globin (HBB) gene on chromosome 11. However, people with the same genetic mutation display a wide range of clinical phenotypes. Fetal hemoglobin (HbF) expression is an important genetic modifier of SCD complications leading to milder symptoms and improved long-term survival. Therefore, we performed a genome-wide association study (GWAS) using a case-control experimental design in 244 African Americans with SCD to discover genetic factors associated with HbF expression. The case group consisted of subjects with HbF≥8.6% (133 samples) …

Trends In Survival Of Chronic Lymphocytic Leukemia Patients In Germany And The Usa In The First Decade Of The Twenty-First Century., Dianne Pulte, Felipe A Castro, Lina Jansen, Sabine Luttmann, Bernd Holleczek, Alice Nennecke, Meike Ressing, Alexander Katalinic, Hermann Brenner

Cardeza Foundation for Hematologic Research

BACKGROUND: Recent population-based studies in the United States of America (USA) and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL) diagnosed in the early twenty-first century. Here, we examine the survival for patients diagnosed with CLL in Germany in 1997-2011.

METHODS: Data were extracted from 12 cancer registries in Germany and compared to the data from the USA. Period analysis was used to estimate 5- and 10-year relative survival (RS).

RESULTS: Five- and 10-year RS estimates in 2009-2011 of 80.2 and 59.5%, respectively, in Germany and 82.4 and 64.7%, respectively, in the USA were …

Conjugate Haemophilus Influenzae Type B Vaccines For Sickle Cell Disease., Slimane Allali, Martin Chalumeau, Odile Launay, Samir K. Ballas, Mariane De Montalembert

Cardeza Foundation for Hematologic Research

BACKGROUND: People affected with sickle cell disease are at high risk of infection from Haemophilus influenzae type b. Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Haemophilus influenzae type b remains one of the most common cause of bacteraemias in children with sickle cell disease. The increased uptake of this conjugate vaccination may substantially improve the survival of children with sickle cell disease.

OBJECTIVES: The primary objective was …

Safety And Efficacy Of Blood Exchange Transfusion For Priapism Complicating Sickle Cell Disease., Samir K. Ballas, David Lyon

Cardeza Foundation for Hematologic Research

BACKGROUND: Priapism is unwanted painful penile erection that affects about 36% of boys and men with sickle cell disease (SCD) most of whom have sickle cell anemia. Clinically, priapism could be stuttering, minor, or major. The first two types are mild, last < 4 h, are usually treated at home, have good prognosis with normal sexual function. The major type of priapism lasts >4 h, associated with severe pain, requires hospitalization; often does not respond to medical treatment and may require shunt surgery. Untreated major priapism and surgical intervention often cause impotence. In this study, we report our 15-year experience in treating adult patients with SCD and major priapism with blood exchange transfusion after being refractory to other medical therapies.

METHODS: …

The Paradox Of The Serrated Sickle Erythrocyte: The Importance Of The Red Blood Cell Membrane Topography., Samir K. Ballas, Philippe Connes

Cardeza Foundation for Hematologic Research

Red blood cell rheology and adhesiveness play a key role in the occurrence of vaso-occlusive like events in sickle cell anemia. The present paper reviews counter-intuitive findings supporting that rigid and serrated sickle red blood cells do not initiate vaso-occlusion. Instead, the less rigid red blood cells could initiate vaso-occlusion because of their increased adhesiveness to the vascular wall. We suspect that stiffness of sickle erythrocytes and the topography of RBC membrane are factors affecting adhesion to the endothelium.

Off-Target V(D)J Recombination Drives Lymphomagenesis And Is Escalated By Loss Of The Rag2 C Terminus., Martina Mijušković, Yi-Fan Chou, Vered Gigi, Cory R Lindsay, Olga Shestova, Susanna M Lewis, David B Roth

Cardeza Foundation for Hematologic Research

Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification.

Risk Factors Of Pulmonary Hypertension In Brazilian Patients With Sickle Cell Anemia., Clarisse Lopes De Castro Lobo, Emilia Matos Do Nascimento, Renato Abelha, Ana Maria Mach Queiroz, Philippe Connes, Gilberto Perez Cardoso, Samir K. Ballas

Cardeza Foundation for Hematologic Research

This study was a prospective cross-sectional cohort study of 125 patients with sickle cell anemia (SS) between the ages of 16 to 60 years. Enrolled patients were followed-up prospectively for 15 months. Demographic, clinical, hematological and routine biochemical data were obtained on all patients. Six-minute walk test and Doppler Echocardiography were performed on all patients. A tricuspid regurgitant jet velocity (TRJV) < 2.5 m/sec was considered normal, 2.5 ≤ TRJV ≤ 3.0 was considered mild-moderate and > 3.0 m/sec, severe. Patients with abnormal TRJV were significantly older and more anemic, had significantly higher lactate dehydrogenase (LDH) levels, reticulocyte count and incidence of death. The logistic multimodal model implemented for the 125 patients indicated that age was …

Clinical Utility Of Lactate Dehydrogenase In Determining The Severity Of Hemolysis In Sickle Cell Anemia., Samir K. Ballas

Cardeza Foundation for Hematologic Research

No abstract provided.

Emerging Drugs For Sickle Cell Anemia., Priya C Singh, Samir K. Ballas

Cardeza Foundation for Hematologic Research

INTRODUCTION: The search for effective therapeutic interventions for sickle cell disease (SCD) has been an ongoing endeavor for over 50 years. During this period, only hydroxyurea (HU), which received US FDA approval in February 1998, was identified as an effective therapeutic agent in preventing or ameliorating the frequency of vaso-occlusive crises, acute chest syndrome and the need for blood transfusion. Approximately 25% of patients with sickle cell anemia (SCA), however, do not respond to HU and some patients experiencing serious side effects of this chemotherapeutic agent. Nevertheless, the success of HU opened the sluice gates to identify other effective drug …

Morphine For The Treatment Of Pain In Sickle Cell Disease., Mihir Gupta, Lilian Msambichaka, Samir K. Ballas, Kalpna Gupta

Cardeza Foundation for Hematologic Research

Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. …

Deferiprone Versus Deferoxamine In Sickle Cell Disease: Results From A 5-Year Long-Term Italian Multi-Center Randomized Clinical Trial., Giusi Calvaruso, Angela Vitrano, Rosario Di Maggio, Samir K. Ballas, Martin H Steinberg, Paolo Rigano, Massimiliano Sacco, Paul Telfer, Disma Renda, Rita Barone, Aurelio Maggio

Cardeza Foundation for Hematologic Research

Blood transfusion and iron chelation currently represent a supportive therapy to manage anemia, vasculopathy and vaso-occlusion crises in Sickle-Cell-Disease. Here we describe the first 5-year long-term randomized clinical trial comparing Deferiprone versus Deferoxamine in patients with Sickle-Cell-Disease. The results of this study show that Deferiprone has the same effectiveness as Deferoxamine in decreasing body iron burden, measured as repeated measurements of serum ferritin concentrations on the same patient over 5-years and analyzed according to the linear mixed-effects model (LMM) (p=0.822). Both chelators are able to decrease, significantly, serum ferritin concentrations, during 5-years, without any effect on safety (p=0.005). Moreover, although …

Racial Differences In Human Platelet Par4 Reactivity Reflect Expression Of Pctp And Mir-376c., Leonard Edelstein, Lukas M Simon, Raúl Teruel Montoya, Michael Holinstat, Edward S Chen, Angela Bergeron, Xianguo Kong, Srikanth Nagalla, Narla Mohandas, David E Cohen, Jing-Fei Dong, Chad Shaw, Paul Bray

Cardeza Foundation for Hematologic Research

Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. Platelet aggregation and calcium mobilization induced by the PAR4 thrombin receptor were significantly greater in black subjects. Numerous differentially expressed RNAs were associated with both race and PAR4 reactivity, including PCTP (encoding phosphatidylcholine transfer protein), and platelets from black subjects expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked PAR4- but not PAR1-mediated activation of platelets and megakaryocytic cell lines. miR-376c levels were differentially expressed by race and …

Neuropathy, Neuropathic Pain, And Sickle Cell Disease., Samir K. Ballas, Deepika S Darbari

Cardeza Foundation for Hematologic Research

No abstract provided.

Erosive Arthritis And Hepatic Granuloma Formation Induced By Peptidoglycan Polysaccharide In Rats Is Aggravated By Prasugrel Treatment., Analia E Garcia, Mario C Rico, Elisabetta Liverani, Raul A Dela Cadena, Paul F. Bray, Satya P Kunapuli

Cardeza Foundation for Hematologic Research

Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS) in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with …

The Complex Transcriptional Landscape Of The Anucleate Human Platelet., Paul F. Bray, Steven E. Mckenzie, Leonard Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Yi Jing, Eric R. Londin, Phillipe Loher, Huang-Wen Chen, Paolo Fortina, Isidore Rigoutsos

Cardeza Foundation for Hematologic Research

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts.

RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (<40 >nucleotides) profiles. Analysis of ~1 billion reads revealed that coding …

Newer Agents In Antiplatelet Therapy: A Review., Jennifer Yeung, Michael Holinstat

Cardeza Foundation for Hematologic Research

Antiplatelet therapy remains the mainstay in preventing aberrant platelet activation in pathophysiological conditions such as myocardial infarction, ischemia, and stroke. Although there has been significant advancement in antiplatelet therapeutic approaches, aspirin still remains the gold standard treatment in the clinical setting. Limitations in safety, efficacy, and tolerability have precluded many of the antiplatelet inhibitors from use in patients. Unforeseen incidences of increased bleeding risk and recurrent arterial thrombosis observed in patients have hampered the development of superior next generation antiplatelet therapies. The pharmacokinetic and pharmacodynamic profiles have also limited the effectiveness of a number of antiplatelet inhibitors currently in use …

Transfection Of Human Platelets With Short Interfering Rna., Wei Hong, Altaf A Kondkar, Srikanth Nagalla, Wolfgang Bergmeier, Ying Jin, Jay Herman, Paul Bray

Cardeza Foundation for Hematologic Research

Platelets contain mRNAs and are capable of translating mRNA into protein, and it has been previously demonstrated that platelets increase their levels of integrin β3 overtime while in blood bank storage conditions. We are unaware of prior attempts to introduce nucleic acids into platelets. Considering the potential clinical and research utility of manipulating platelet gene expression, we tested whether small interfering RNAs (siRNAs) could be transfected into normal human platelets. Multiple conditions were tested, including lipofectamine versus electroporation, different amounts of siRNA, the effect of different buffers and the presence of plasma during transfection, and the time for optimal siRNA …

Differences In Responses Of Platelets To Fluid Shear Stress In Patients With Peripheral Artery Disease (Pad) And Coronary Artery Disease (Cad)., Vijay Nambi, Kay T Kimball, Paul Bray, Angela L Bergeron, Shawna L Johnson, Joel D Morrisett, Changyi Chen, Peter H Lin, Alan B Lumsden, Christie M Ballantyne, Jing-Fei Dong

Cardeza Foundation for Hematologic Research

Information on differences in platelet function between patients with peripheral arterial disease (PAD) and patients with coronary artery disease (CAD) is limited. We sought to examine the differences in the platelets response to shear stress in patients with PAD compared to those with CAD. Men with symptomatic PAD (ankle brachial index [ABI] < 0.9; n = 29) were compared with similarly aged men with CAD (post coronary artery bypass grafting; n = 40) but without PAD. All participants were on aspirin, and none were on clopidogrel. We measured changes in shear-induced platelet aggregation (SIPA) and shear-induced P-selectin expression (SIPE) under fluid shear rates of 5000 and 10,000 s(-1)which are typically found in arterioles and stenosed arteries, respectively. Aggregation was also induced by a combined stimulation of collagen, fluid shear stress, and adenosine diphosphate (ADP) or epinephrine using a platelet function analyzer (PFA-100) as well as optical aggregometry (arachidonic acid, collagen and epinephrine). Analyses of covariance adjusted for age, aspirin dose, and statin use were used to estimate differences between the groups. Values of SIPA at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in the PAD group, while there were no differences between the PAD and CAD groups in SIPE at both fluid shear rates. However, baseline shear-induced P-selectin expression was higher in patients with PAD than CAD (mean fluorescence intensity [MFI] = 2.93 +/- 1.37 vs.1.94 +/- 0.67; p = 0.01), while the percentage increases in SIPA and SIPE at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in patients with CAD when compared to PAD (p < 0.001 for all comparisons). Although there were several similarities in platelet function between men with PAD and men with CAD, significant differences in platelet responses to shear stress were observed in men with PAD when compared to those with CAD. Although the mechanism for these observed differences are not clear, we hypothesize that in vivo platelet activation in PAD patients may contribute to the differences and will need to be further investigated.

Usefulness Of Baseline Lipids And C-Reactive Protein In Women Receiving Menopausal Hormone Therapy As Predictors Of Treatment-Related Coronary Events., Paul Bray, Joseph C Larson, Andrea Z Lacroix, Joann Manson, Marian C Limacher, Jacques E Rossouw, Norman L Lasser, William E Lawson, Marcia L Stefanick, Robert D Langer, Karen L Margolis

Cardeza Foundation for Hematologic Research

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen …

Platelet Hyperreactivity: Predictive And Intrinsic Properties., Paul F. Bray

Cardeza Foundation for Hematologic Research

Platelet thrombi are central to the development of most vascular ischemic events. There is marked interindividual variation in platelet responsiveness, with some subjects displaying platelet hyperreactivity. An increasing number of reports indicate that there are laboratory measures of platelet function that predict clinical thrombotic events. Some, but not all, measures of platelet function are reproducible. Platelet hyperreactivity can be assessed with multiple stimuli in multiple assays and is more likely to be present in women and in subjects who have elevated fibrinogen levels.

Genome-Wide Analysis Of Neuroblastomas Using High-Density Single Nucleotide Polymorphism Arrays., Rani E George, Edward F Attiyeh, Shuli Li, Lisa A Moreau, Donna Neuberg, Cheng Li, Edward A Fox, Matthew Meyerson, Lisa Diller, Paolo Fortina, A Thomas Look, John M Maris

Cardeza Foundation for Hematologic Research

BACKGROUND: Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH) and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP) array.

FINDINGS: Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%). Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016). Chromosome 1p …

Induction Of Beta3-Integrin Gene Expression By Sustained Activation Of The Ras-Regulated Raf-Mek-Extracellular Signal-Regulated Kinase Signaling Pathway., Douglas Woods, Holly Cherwinski, Eleni Venetsanakos, Arun Bhat, Stephan Gysin, Martine Humbert, Paul F. Bray, Vicki L. Saylor, Martin Mcmahon

Cardeza Foundation for Hematologic Research

Alterations in the expression of integrin receptors for extracellular matrix (ECM) proteins are strongly associated with the acquisition of invasive and/or metastatic properties by human cancer cells. Despite this, comparatively little is known of the biochemical mechanisms that regulate the expression of integrin genes in cells. Here we demonstrate that the Ras-activated Raf-MEK-extracellular signal-regulated kinase (ERK) signaling pathway can specifically control the expression of individual integrin subunits in a variety of human and mouse cell lines. Pharmacological inhibition of MEK1 in a number of human melanoma and pancreatic carcinoma cell lines led to reduced cell surface expression of alpha6- and …

The Pl(A2) Polymorphism Of Integrin Beta(3) Enhances Outside-In Signaling And Adhesive Functions., K Vinod Vijayan, Pascal J. Goldschmidt-Clermont, Christine Roos, Paul F. Bray

Cardeza Foundation for Hematologic Research

Genetic factors are believed to influence the development of arterial thromboses. Because integrin alpha(IIb)beta(3) plays a crucial role in thrombus formation, we analyzed receptor adhesive properties using Chinese hamster ovary and human kidney embryonal 293 cells overexpressing the Pl(A1) or Pl(A2) polymorphic forms of alpha(IIb)beta(3). Soluble fibrinogen binding was no different between Pl(A1) and Pl(A2) cells, either in a resting state or when alpha(IIb)beta(3) was activated with anti-LIBS6. Pl(A1) and Pl(A2) cells bound equivalently to immobilized fibronectin. In contrast, significantly more Pl(A2) cells bound to immobilized fibrinogen in an alpha(IIb)beta(3)-dependent manner than did Pl(A1) cells. Disruption of the actin cytoskeleton …

Integrin-Dependent Control Of Translation: Engagement Of Integrin Alphaiibbeta3 Regulates Synthesis Of Proteins In Activated Human Platelets., Ravinder Pabla, Andrew S. Weyrich, Dan A. Dixon, Paul F. Bray, Thomas M. Mcintyre, Stephen M. Prescott, Guy A. Zimmerman

Cardeza Foundation for Hematologic Research

Integrins are widely expressed plasma membrane adhesion molecules that tether cells to matrix proteins and to one another in cell-cell interactions. Integrins also transmit outside-in signals that regulate functional responses of cells, and are known to influence gene expression by regulating transcription. In previous studies we found that platelets, which are naturally occurring anucleate cytoplasts, translate preformed mRNA transcripts when they are activated by outside-in signals. Using strategies that interrupt engagement of integrin alphaIIbbeta3 by fibrinogen and platelets deficient in this integrin, we found that alphaIIbbeta3 regulates the synthesis of B cell lymphoma 3 (Bcl-3) when platelet aggregation is induced …