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Monitoring minimal residual disease in the bone marrow using next generation sequencing.

Abstract
Achieving minimal residual disease (MRD) negativity in the bone marrow is one of the strongest prognostic factors in multiple myeloma. Consequently, MRD testing is routinely performed in clinical trials and moving towards standard of care. This review focuses on the role of next generation sequencing (NGS) of tumor-specific immunoglobulin V(D)J sequences for MRD tracking. The immunoglobulin variable regions are ideal targets for tracking, because every tumor cell shares an identical gene sequence, which is stable over time and generally distinct from the immunoglobulin sequences of normal B-cells. Several excellent assays for NGS-based MRD testing are available, both commercial and community-based, including one that is FDA-approved. These assays can achieve the gold standard analytical sensitivity of one tumor cell per million (10-6), requiring a minimum input of 3 million bone marrow cells. On-going clinical trials will outline how MRD testing should be used to inform dynamic risk-adopted therapy.
AuthorsEven H Rustad, Eileen M Boyle
JournalBest practice & research. Clinical haematology (Best Pract Res Clin Haematol) Vol. 33 Issue 1 Pg. 101149 (03 2020) ISSN: 1532-1924 [Electronic] Netherlands
PMID32139014 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
CopyrightCopyright © 2020 Elsevier Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • DNA, Neoplasm
  • Immunoglobulin Variable Region
Topics
  • Antineoplastic Agents (therapeutic use)
  • Bone Marrow (drug effects, immunology, pathology)
  • Cell Count
  • DNA, Neoplasm (genetics, immunology)
  • High-Throughput Nucleotide Sequencing (methods)
  • Humans
  • Immunoglobulin Variable Region (genetics, immunology)
  • Multiple Myeloma (diagnosis, drug therapy, genetics, immunology)
  • Mutation
  • Neoplasm, Residual
  • Plasma Cells (drug effects, immunology, pathology)
  • Prognosis
  • Recurrence
  • Sensitivity and Specificity
  • V(D)J Recombination (immunology)

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