title: A CD138-independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma.
abstract: CD138 (also termed SDC1) has been the gold-standard surface marker to detect multiple myeloma (MM) cells for decades; however, drug-resistant residual and circulating MM cells were shown to have lower expression of this marker. In this study, we have shown that residual MM cells following bortezomib treatment are hypoxic. This combination of drug exposure and hypoxia down-regulates their CD138 expression, thereby making this marker unsuitable for detecting residual or other hypoxic MM cells, such as circulating tumour cells, in MM. Hence, we developed an alternative biomarker set which detects myeloma cells independent of their hypoxic and CD138 expression status in vitro, in vivo and in primary MM patients. The new markers were able to identify a clonal CD138-negative population as minimal residual disease in the bone marrow and peripheral blood of MM patients. Further investigation to characterize the role of this population as a prognostic marker in MM is warranted.
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Muz
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Pilar
authors.initials: P
authors.lastname: de la Puente
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Feda
authors.initials: F
authors.lastname: Azab
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Micah John
authors.initials: MJ
authors.lastname: Luderer
authors.affiliation: Section of Stem Cell Transplant and Leukemia, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: King
authors.affiliation: Section of Stem Cell Transplant and Leukemia, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Abdel Kareem
authors.initials: AK
authors.lastname: Azab
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000097:blood* / Q000473:pathology; D009363:Neoplasm Proteins / Q000097:blood*; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D053668:Syndecan-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C508241:SDC1 protein, human; D053668:Syndecan-1
keywords: cell surface antigens; diagnostic haematology; flow cytometry; haematological malignancy; minimal residual disease; multiple myeloma