ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Advanced Search

RNAseq Transcriptome Analysis of Bone Marrow CD138+ Plasma Cell Responses to Carfilzomib Monotherapy Desensitization.

J. Driscoll, B. Aronow, S. Tremblay, R. Alloway, E. Woodle.

Medicine, Surgery, Biomedical Informatics, U of Cincinnati, Cincinnati Children's, Cincinnati, OH.

Meeting: 2016 American Transplant Congress

Abstract number: 323

Keywords: B cells, Gene expression, Genomics, HLA antibodies

Session Information

Date: Monday, June 13, 2016

Session Name: Concurrent Session: Kidney: Desensitization

Session Time: 4:30pm-6:00pm

 Presentation Time: 5:30pm-5:42pm

Location: Room 304

Related Abstracts
  • Recall Alloantibody Production Is Driven by CD138+ Cells Proliferating in the Spleens: An Indication for Long-Lived Plasma Cell Activities and Potential Therapeutic Target.
  • Interrogation of Plasma Cell-Rich Acute Rejection in Human Kidney Allografts by Whole Transcriptome Sequencing

Purpose: Prior studies indicate that bone marrow resident plasma cells (BMRPCs) demonstrate varying sensitivity to proteasome inhibition (PI). Effects of carfilzomib (CFZ) monotherapy desensitization on CD138+ BMRPC gene expression were analyzed.

Methods: HLA-sensitized transplant candidates received escalating CFZ doses (20, 27, 36 mg/m2) with BM aspirates performed before and after CFZ. CD138+ BMRPCs were isolated to >98% purity;total RNA was analyzed on Ilumina TruSeq NGS platform (30 million reads/sample with paired end 75 bp sequencing). Strongly and differentially expressed gene sets were clustered and evaluated using enrichment and prior knowledge-based network and interactions analyses using ToppGene Suite (toppgene.cchmc.org/).

Results: CFZ therapy reduced CD138+ BMRPC by a mean of 72%.RNAseq analysis of CD138+ BMRPC identified 2,024 differentially expressed transcripts corresponding to 1755 genes (1273 upregulated and 482 down regulated) following CFZ. Network analysis revealed strong shifts in B-cell and plasma cell (PC) genes; PC and B cell development genes were exclusively upregulated whereas genes associated with mature B cells were both up-regulated and down-regulated. Upregulated genes including many associated with 1) ubiquitin+proteasome system (UPS), 2) apoptosis negative regulation, and 3) negative regulation of cell-cycle control. Genes encoding proteolysis in the immunoproteasome (IP) (PSMB8, PSMB9, PSM10) were upregulated more than those in the constitutive proteasome (CP), indicating potential changes in PI sensitivity. In vitro assessment of chymotrypsin-like activity in BMRPCs after CFZ treatment revealed reduced chymotryptic-like inhibition by CFZ, bortezomib and ixazomib, but increased inhibition with an IP-specific inhibitor. These results indicate a shift toward IP-specific proteolysis may mediate relative CFZ resistance in surviving BMRPCs.

Conclusions: This first RNAseq expression profile analysis of untransformed, human CD138+ BMRPCs revealed wide-ranging PI-induced effects on genes controlling B cell differentiation into PCs and high connectivity and dependence on genes associated with UPS and autophagy. Additional in vitro studies indicated changes from CP to IP proteolytic capacity post-CFZ. These studies suggest several new strategies to personalize and enhance PI-based PC depletional therapy, such as sequential therapy with CP and IP-selective inhibitors.

CITATION INFORMATION: Driscoll J, Aronow B, Tremblay S, Alloway R, Woodle E. RNAseq Transcriptome Analysis of Bone Marrow CD138+ Plasma Cell Responses to Carfilzomib Monotherapy Desensitization. Am J Transplant. 2016;16 (suppl 3).

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Driscoll J, Aronow B, Tremblay S, Alloway R, Woodle E. RNAseq Transcriptome Analysis of Bone Marrow CD138+ Plasma Cell Responses to Carfilzomib Monotherapy Desensitization. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/rnaseq-transcriptome-analysis-of-bone-marrow-cd138-plasma-cell-responses-to-carfilzomib-monotherapy-desensitization/. Accessed January 22, 2021.

« Back to 2016 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Penis Transplantation: First U.S. Experience.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
    • Penis Transplantation: First U.S. Experience.
    • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
    • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
    • Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus: A Case Report
    • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes

    Visit Our Partner Sites

    American Transplant Congress (ATC)

    Visit the official site for the American Transplant Congress »

    American Journal of Transplantation

    The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

    American Society of Transplantation (AST)

    An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

    American Society of Transplant Surgeons (ASTS)

    The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

    Copyright © 2013-2021 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

    Privacy Policy

    loading Cancel
    Post was not sent - check your email addresses!
    Email check failed, please try again
    Sorry, your blog cannot share posts by email.
    This site uses cookies: Find out more.