<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01735565</url>
  </required_header>
  <id_info>
    <org_study_id>56286</org_study_id>
    <nct_id>NCT01735565</nct_id>
  </id_info>
  <brief_title>Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplant</brief_title>
  <official_title>Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplant</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective observational study to determine the point after bone marrow transplant&#xD;
      in adults and children at which the neutrophils derived from the transplanted stem cells are&#xD;
      competent to form functional neutrophil extracellular traps (NETs). Furthermore, given the&#xD;
      importance of platelet function for NET formation, we also plan to examine platelet&#xD;
      activation and function as well as the platelet transcriptome using the same clinical&#xD;
      samples.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background and Introduction&#xD;
&#xD;
      The role of the human polymorphonuclear leukocytes (PMNs) in the acute inflammatory response&#xD;
      is well documented. PMNs play a fundamental role in the innate immune response and are&#xD;
      rapidly recruited to areas of injury or inflammation where they participate in bacterial&#xD;
      phagocytosis and killing. Disorders associated with a deficiency or impairment of PMN&#xD;
      function (neutropenia, chronic granulomatous disease (CGD), leukocyte adhesion deficiency)&#xD;
      predispose to infections with bacteria and fungi. Regulation of this potent component of the&#xD;
      acute inflammatory response is imperative to prevent overwhelming infections often associated&#xD;
      with morbidity and mortality.&#xD;
&#xD;
      Recently, neutrophils isolated from healthy adult donors were shown to undergo programmed&#xD;
      cell death distinct from apoptosis and necrosis to form neutrophil extracellular traps&#xD;
      (NETs). NETs are extensive lattices of extracellular DNA and chromatin decorated with&#xD;
      anti-microbial proteins and degradative enzymes such as myeloperoxidase and neutrophil&#xD;
      elastase (NE). NETs effect extracellular killing of bacteria and fungi. The laboratory of&#xD;
      Christian Yost, MD recently characterized impaired NET formation as a novel innate immune&#xD;
      deficiency of human newborn infants and showed that PMNs isolated from the cord blood of&#xD;
      newborn infants, both term and preterm, demonstrated impaired NET formation and extracellular&#xD;
      bacterial killing as compared to PMNs isolated from healthy adults. However, the timing for&#xD;
      developmental maturation of newborn infant PMN NET formation remains unknown.&#xD;
&#xD;
      Stem cells for bone marrow transplants originate from cord blood, peripheral stem cells, or&#xD;
      bone marrow stem cells. Regardless of the source of these stem cells, patients receiving a&#xD;
      bone marrow transplant are essentially building a new immune system, as if they were a&#xD;
      newborn baby. Immune system reconstitution is a continuous process whose components can take&#xD;
      up to 1 to 2 years to fully recover. Severe infections in bone marrow transplant patients&#xD;
      occur and may be associated with deficient PMN NET formation by way of impaired extracellular&#xD;
      bacterial containment and killing. We hypothesize that the increased risk of infection&#xD;
      attributed to bone marrow transplant recipients results, in part, from deficient PMN NET&#xD;
      formation by the nascent, post-engraftment immune system which is molecularly and&#xD;
      functionally similar to that of a newborn baby. We plan to determine the point after&#xD;
      transplant at which the neutrophils derived from the transplanted stem cells are competent to&#xD;
      form functional NETs. Furthermore, given the importance of platelet function for NET&#xD;
      formation, we also plan to examine platelet activation and function as well as the platelet&#xD;
      transcriptome using the same clinical samples.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Post-engraftment maturation of NET formation</measure>
    <time_frame>1 year</time_frame>
    <description>The time to post-engraftment maturation of NET formation capability in PMNs isolated from pediatric and adult patients undergoing bone marrow transplantation will be measured by serial blood sampling/analysis over the course of a year after transplant.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Post-engraftment platelet function</measure>
    <time_frame>1 year</time_frame>
    <description>Post-engraftment platelet function, transcriptome, and their potential influence on NET formation by PMNs will be measured by serial blood sampling/analysis over the course of a year after transplant.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">23</enrollment>
  <condition>Bone Marrow Transplant</condition>
  <arm_group>
    <arm_group_label>Post bone marrow transplant</arm_group_label>
    <description>Patients who are undergoing bone marrow transplant, as well as patients who have completed a bone marrow transplant within the previous year.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who are undergoing bone marrow transplant, as well as patients who have completed&#xD;
        a bone marrow transplant within the previous year at Huntsman Cancer Institute and Primary&#xD;
        Children's Medical Center will be identified as possible participants.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Within one year of bone marrow transplant&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No specific exclusion criteria&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christian Yost, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Primary Children's Medical Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Dinauer MC, Lekstrom-Himes JA, Dale DC. Inherited Neutrophil Disorders: Molecular Basis and New Therapies. Hematology Am Soc Hematol Educ Program. 2000:303-318. doi: 10.1182/asheducation-2000.1.303.</citation>
    <PMID>11701548</PMID>
  </reference>
  <reference>
    <citation>Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science. 2004 Mar 5;303(5663):1532-5. doi: 10.1126/science.1092385.</citation>
    <PMID>15001782</PMID>
  </reference>
  <reference>
    <citation>Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006 Mar;6(3):173-82. doi: 10.1038/nri1785.</citation>
    <PMID>16498448</PMID>
  </reference>
  <reference>
    <citation>Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007 Jan 15;176(2):231-41. doi: 10.1083/jcb.200606027. Epub 2007 Jan 8.</citation>
    <PMID>17210947</PMID>
  </reference>
  <reference>
    <citation>Buchanan JT, Simpson AJ, Aziz RK, Liu GY, Kristian SA, Kotb M, Feramisco J, Nizet V. DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps. Curr Biol. 2006 Feb 21;16(4):396-400. doi: 10.1016/j.cub.2005.12.039.</citation>
    <PMID>16488874</PMID>
  </reference>
  <reference>
    <citation>Urban CF, Reichard U, Brinkmann V, Zychlinsky A. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol. 2006 Apr;8(4):668-76. doi: 10.1111/j.1462-5822.2005.00659.x.</citation>
    <PMID>16548892</PMID>
  </reference>
  <reference>
    <citation>Bianchi M, Hakkim A, Brinkmann V, Siler U, Seger RA, Zychlinsky A, Reichenbach J. Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood. 2009 Sep 24;114(13):2619-22. doi: 10.1182/blood-2009-05-221606. Epub 2009 Jun 18.</citation>
    <PMID>19541821</PMID>
  </reference>
  <reference>
    <citation>Bianchi M, Niemiec MJ, Siler U, Urban CF, Reichenbach J. Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol. 2011 May;127(5):1243-52.e7. doi: 10.1016/j.jaci.2011.01.021. Epub 2011 Mar 3.</citation>
    <PMID>21376380</PMID>
  </reference>
  <reference>
    <citation>Yost CC, Cody MJ, Harris ES, Thornton NL, McInturff AM, Martinez ML, Chandler NB, Rodesch CK, Albertine KH, Petti CA, Weyrich AS, Zimmerman GA. Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood. 2009 Jun 18;113(25):6419-27. doi: 10.1182/blood-2008-07-171629. Epub 2009 Feb 12.</citation>
    <PMID>19221037</PMID>
  </reference>
  <reference>
    <citation>Marcos V, Nussbaum C, Vitkov L, Hector A, Wiedenbauer EM, Roos D, Kuijpers T, Krautgartner WD, Genzel-Boroviczeny O, Sperandio M, Hartl D. Delayed but functional neutrophil extracellular trap formation in neonates. Blood. 2009 Nov 26;114(23):4908-11; author reply 4911-2. doi: 10.1182/blood-2009-09-242388. No abstract available.</citation>
    <PMID>19965699</PMID>
  </reference>
  <reference>
    <citation>Kraemer BF, Campbell RA, Schwertz H, Cody MJ, Franks Z, Tolley ND, Kahr WH, Lindemann S, Seizer P, Yost CC, Zimmerman GA, Weyrich AS. Novel anti-bacterial activities of beta-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation. PLoS Pathog. 2011 Nov;7(11):e1002355. doi: 10.1371/journal.ppat.1002355. Epub 2011 Nov 10.</citation>
    <PMID>22102811</PMID>
  </reference>
  <reference>
    <citation>Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, Keys EM, Allen-Vercoe E, Devinney R, Doig CJ, Green FH, Kubes P. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007 Apr;13(4):463-9. doi: 10.1038/nm1565. Epub 2007 Mar 25.</citation>
    <PMID>17384648</PMID>
  </reference>
  <reference>
    <citation>Rondina MT, Brewster B, Grissom CK, Zimmerman GA, Kastendieck DH, Harris ES, Weyrich AS. In vivo platelet activation in critically ill patients with primary 2009 influenza A(H1N1). Chest. 2012 Jun;141(6):1490-1495. doi: 10.1378/chest.11-2860. Epub 2012 Mar 1.</citation>
    <PMID>22383669</PMID>
  </reference>
  <reference>
    <citation>Rondina MT, Schwertz H, Harris ES, Kraemer BF, Campbell RA, Mackman N, Grissom CK, Weyrich AS, Zimmerman GA. The septic milieu triggers expression of spliced tissue factor mRNA in human platelets. J Thromb Haemost. 2011 Apr;9(4):748-58. doi: 10.1111/j.1538-7836.2011.04208.x.</citation>
    <PMID>21255247</PMID>
  </reference>
  <reference>
    <citation>Denis MM, Tolley ND, Bunting M, Schwertz H, Jiang H, Lindemann S, Yost CC, Rubner FJ, Albertine KH, Swoboda KJ, Fratto CM, Tolley E, Kraiss LW, McIntyre TM, Zimmerman GA, Weyrich AS. Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell. 2005 Aug 12;122(3):379-91. doi: 10.1016/j.cell.2005.06.015.</citation>
    <PMID>16096058</PMID>
  </reference>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>November 22, 2012</study_first_submitted>
  <study_first_submitted_qc>November 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>August 9, 2016</last_update_submitted>
  <last_update_submitted_qc>August 9, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 11, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NET formation</keyword>
  <keyword>neutraphil extracellular traps</keyword>
  <keyword>post-engraftment immune system</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01735565
org study id: 56286
nct id: NCT01735565
lead sponsor: 
collaborator: 
has dmc: No
This is a prospective observational study to determine the point after bone marrow transplant
      in adults and children at which the neutrophils derived from the transplanted stem cells are
      competent to form functional neutrophil extracellular traps (NETs). Furthermore, given the
      importance of platelet function for NET formation, we also plan to examine platelet
      activation and function as well as the platelet transcriptome using the same clinical
      samples.
Background and Introduction

      The role of the human polymorphonuclear leukocytes (PMNs) in the acute inflammatory response
      is well documented. PMNs play a fundamental role in the innate immune response and are
      rapidly recruited to areas of injury or inflammation where they participate in bacterial
      phagocytosis and killing. Disorders associated with a deficiency or impairment of PMN
      function (neutropenia, chronic granulomatous disease (CGD), leukocyte adhesion deficiency)
      predispose to infections with bacteria and fungi. Regulation of this potent component of the
      acute inflammatory response is imperative to prevent overwhelming infections often associated
      with morbidity and mortality.

      Recently, neutrophils isolated from healthy adult donors were shown to undergo programmed
      cell death distinct from apoptosis and necrosis to form neutrophil extracellular traps
      (NETs). NETs are extensive lattices of extracellular DNA and chromatin decorated with
      anti-microbial proteins and degradative enzymes such as myeloperoxidase and neutrophil
      elastase (NE). NETs effect extracellular killing of bacteria and fungi. The laboratory of
      Christian Yost, MD recently characterized impaired NET formation as a novel innate immune
      deficiency of human newborn infants and showed that PMNs isolated from the cord blood of
      newborn infants, both term and preterm, demonstrated impaired NET formation and extracellular
      bacterial killing as compared to PMNs isolated from healthy adults. However, the timing for
      developmental maturation of newborn infant PMN NET formation remains unknown.

      Stem cells for bone marrow transplants originate from cord blood, peripheral stem cells, or
      bone marrow stem cells. Regardless of the source of these stem cells, patients receiving a
      bone marrow transplant are essentially building a new immune system, as if they were a
      newborn baby. Immune system reconstitution is a continuous process whose components can take
      up to 1 to 2 years to fully recover. Severe infections in bone marrow transplant patients
      occur and may be associated with deficient PMN NET formation by way of impaired extracellular
      bacterial containment and killing. We hypothesize that the increased risk of infection
      attributed to bone marrow transplant recipients results, in part, from deficient PMN NET
      formation by the nascent, post-engraftment immune system which is molecularly and
      functionally similar to that of a newborn baby. We plan to determine the point after
      transplant at which the neutrophils derived from the transplanted stem cells are competent to
      form functional NETs. Furthermore, given the importance of platelet function for NET
      formation, we also plan to examine platelet activation and function as well as the platelet
      transcriptome using the same clinical samples.
observational model: Cohort
time perspective: Prospective
measure: Post-engraftment maturation of NET formation
time frame: 1 year
description: The time to post-engraftment maturation of NET formation capability in PMNs isolated from pediatric and adult patients undergoing bone marrow transplantation will be measured by serial blood sampling/analysis over the course of a year after transplant.
measure: Post-engraftment platelet function
time frame: 1 year
description: Post-engraftment platelet function, transcriptome, and their potential influence on NET formation by PMNs will be measured by serial blood sampling/analysis over the course of a year after transplant.
arm group label: Post bone marrow transplant
description: Patients who are undergoing bone marrow transplant, as well as patients who have completed a bone marrow transplant within the previous year.
Whole blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Christian Yost, MD
role: Principal Investigator
affiliation: University of Utah
facility: 
facility: 
facility: 
country: United States
citation: Dinauer MC, Lekstrom-Himes JA, Dale DC. Inherited Neutrophil Disorders: Molecular Basis and New Therapies. Hematology Am Soc Hematol Educ Program. 2000:303-318. doi: 10.1182/asheducation-2000.1.303.
PMID: 11701548
citation: Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science. 2004 Mar 5;303(5663):1532-5. doi: 10.1126/science.1092385.
PMID: 15001782
citation: Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006 Mar;6(3):173-82. doi: 10.1038/nri1785.
PMID: 16498448
citation: Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007 Jan 15;176(2):231-41. doi: 10.1083/jcb.200606027. Epub 2007 Jan 8.
PMID: 17210947
citation: Buchanan JT, Simpson AJ, Aziz RK, Liu GY, Kristian SA, Kotb M, Feramisco J, Nizet V. DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps. Curr Biol. 2006 Feb 21;16(4):396-400. doi: 10.1016/j.cub.2005.12.039.
PMID: 16488874
citation: Urban CF, Reichard U, Brinkmann V, Zychlinsky A. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol. 2006 Apr;8(4):668-76. doi: 10.1111/j.1462-5822.2005.00659.x.
PMID: 16548892
citation: Bianchi M, Hakkim A, Brinkmann V, Siler U, Seger RA, Zychlinsky A, Reichenbach J. Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood. 2009 Sep 24;114(13):2619-22. doi: 10.1182/blood-2009-05-221606. Epub 2009 Jun 18.
PMID: 19541821
citation: Bianchi M, Niemiec MJ, Siler U, Urban CF, Reichenbach J. Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol. 2011 May;127(5):1243-52.e7. doi: 10.1016/j.jaci.2011.01.021. Epub 2011 Mar 3.
PMID: 21376380
citation: Yost CC, Cody MJ, Harris ES, Thornton NL, McInturff AM, Martinez ML, Chandler NB, Rodesch CK, Albertine KH, Petti CA, Weyrich AS, Zimmerman GA. Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood. 2009 Jun 18;113(25):6419-27. doi: 10.1182/blood-2008-07-171629. Epub 2009 Feb 12.
PMID: 19221037
citation: Marcos V, Nussbaum C, Vitkov L, Hector A, Wiedenbauer EM, Roos D, Kuijpers T, Krautgartner WD, Genzel-Boroviczeny O, Sperandio M, Hartl D. Delayed but functional neutrophil extracellular trap formation in neonates. Blood. 2009 Nov 26;114(23):4908-11; author reply 4911-2. doi: 10.1182/blood-2009-09-242388. No abstract available.
PMID: 19965699
citation: Kraemer BF, Campbell RA, Schwertz H, Cody MJ, Franks Z, Tolley ND, Kahr WH, Lindemann S, Seizer P, Yost CC, Zimmerman GA, Weyrich AS. Novel anti-bacterial activities of beta-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation. PLoS Pathog. 2011 Nov;7(11):e1002355. doi: 10.1371/journal.ppat.1002355. Epub 2011 Nov 10.
PMID: 22102811
citation: Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, Keys EM, Allen-Vercoe E, Devinney R, Doig CJ, Green FH, Kubes P. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007 Apr;13(4):463-9. doi: 10.1038/nm1565. Epub 2007 Mar 25.
PMID: 17384648
citation: Rondina MT, Brewster B, Grissom CK, Zimmerman GA, Kastendieck DH, Harris ES, Weyrich AS. In vivo platelet activation in critically ill patients with primary 2009 influenza A(H1N1). Chest. 2012 Jun;141(6):1490-1495. doi: 10.1378/chest.11-2860. Epub 2012 Mar 1.
PMID: 22383669
citation: Rondina MT, Schwertz H, Harris ES, Kraemer BF, Campbell RA, Mackman N, Grissom CK, Weyrich AS, Zimmerman GA. The septic milieu triggers expression of spliced tissue factor mRNA in human platelets. J Thromb Haemost. 2011 Apr;9(4):748-58. doi: 10.1111/j.1538-7836.2011.04208.x.
PMID: 21255247
citation: Denis MM, Tolley ND, Bunting M, Schwertz H, Jiang H, Lindemann S, Yost CC, Rubner FJ, Albertine KH, Swoboda KJ, Fratto CM, Tolley E, Kraiss LW, McIntyre TM, Zimmerman GA, Weyrich AS. Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell. 2005 Aug 12;122(3):379-91. doi: 10.1016/j.cell.2005.06.015.
PMID: 16096058
responsible party type: Sponsor