Mass spectrometry-based method targeting Ig variable regions for assessment of minimal residual disease in multiple myeloma Journal Article

Authors: Martins, C. O.; Huet, S.; Yi, S. S.; Ritorto, M. S.; Landgren, O.; Dogan, A.; Chapman, J. R.
Article Title: Mass spectrometry-based method targeting Ig variable regions for assessment of minimal residual disease in multiple myeloma
Abstract: Multiple myeloma is a systemic malignancy of monoclonal plasma cells that accounts for 10% of hematologic cancers. With development of highly effective therapies for multiple myeloma, minimal residual disease (MRD) assessment has emerged as an important end point for management decisions. Currently, serologic assays lack the sensitivity for MRD assessment, and invasive bone marrow sampling with flow cytometry or molecular methods has emerged as the gold standard. We report a sensitive and robust targeted mass spectrometry proteomics method to detect MRD in serum, without the need of invasive, sequential bone marrow aspirates. The method detects Ig-derived clonotypic tryptic peptides predicted by sequencing the clonal plasma cell Ig genes. A heavy isotope-labeled Ig internal standard is added to patient serum at a known concentration, the Ig is enriched in a light chain type specific manner, and proteins are digested and analyzed by targeted mass spectrometry. Peptides from the constant regions of the λ or κ light chains, Ig heavy chains, and clonotypic peptides unique to the patient monoclonal Igs are targeted. This technique is highly sensitive and specific for the patient-specific monoclonal Igs, even in samples negative by multiparametric flow cytometry. Our method can accurately and precisely detect monoclonal protein in serum of patients treated for myeloma and has broad implications for management of hematologic patients. © 2020 Association for Molecular Pathology and American Society for Investigative Pathology
Keywords: clinical article; controlled study; human cell; comparative study; flow cytometry; multiple myeloma; cohort analysis; proteomics; monoclonal antibody; plasma cell; immunoglobulin heavy chain; immunoglobulin variable region; messenger rna; bone marrow biopsy; minimal residual disease; immunoglobulin kappa chain; immunoglobulin lambda chain; immunoglobulin light chain; m protein; immunoglobulin blood level; cloning; liquid chromatography-mass spectrometry; radiolabeling; human; article; rna sequencing; daratumumab
Journal Title: Journal of Molecular Diagnostics
Volume: 22
Issue: 7
ISSN: 1525-1578
Publisher: Elsevier Science, Inc.  
Date Published: 2020-07-01
Start Page: 901
End Page: 911
Language: English
DOI: 10.1016/j.jmoldx.2020.04.002
PUBMED: 32302778
PROVIDER: scopus
PMCID: PMC7338887
Notes: Article -- Export Date: 1 July 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. San S Yi
    14 Yi
  2. Ahmet Dogan
    393 Dogan
  3. Carl Ola Landgren
    334 Landgren
  4. Sarah Huet
    3 Huet