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The myeloma stem cell concept, revisited: from phenomenology to operational terms.
- Source :
-
Haematologica [Haematologica] 2016 Dec; Vol. 101 (12), pp. 1451-1459. Date of Electronic Publication: 2016 Nov 10. - Publication Year :
- 2016
-
Abstract
- The concept of the myeloma stem cell may have important therapeutic implications, yet its demonstration has been hampered by a lack of consistency in terms and definitions. Here, we summarize the current documentation and propose single-cell in vitro studies for future translational studies. By the classical approach, a CD19 <superscript>-</superscript> /CD45 <superscript>low/-</superscript> /CD38 <superscript>high</superscript> /CD138 <superscript>+</superscript> malignant plasma cell, but not the CD19 <superscript>+</superscript> /CD38 <superscript>low/-</superscript> memory B cell compartment, is enriched for tumorigenic cells that initiate myeloma in xenografted immunodeficient mice, supporting that myeloma stem cells are present in the malignant PC compartment. Using a new approach, analysis of c-DNA libraries from CD19 <superscript>+</superscript> /CD27 <superscript>+</superscript> /CD38 <superscript>-</superscript> single cells has identified clonotypic memory B cell, suggested to be the cell of origin. This is consistent with multiple myeloma being a multistep hierarchical process before or during clinical presentation. We anticipate that further characterization will require single cell geno- and phenotyping combined with clonogenic assays. To implement such technologies, we propose a revision of the concept of a myeloma stem cell by including operational in vitro assays to describe the cellular components of origin, initiation, maintenance, and evolution of multiple myeloma. These terms are in accordance with recent (2012) consensus statements on the definitions, assays, and nomenclature of cancer stem cells, which is technically precise without completely abolishing established terminology. We expect that this operational model will be useful for future reporting of parameters used to identify and characterize the multiple myeloma stem cells. We strongly recommend that these parameters include validated standard technologies, reproducible assays, and, most importantly, supervised prospective sampling of selected biomaterial which reflects clinical stages, disease spectrum, and therapeutic outcome. This framework is key to the characterization of the cellular architecture of multiple myeloma and its use in precision medicine.<br /> (Copyright© Ferrata Storti Foundation.)
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
B-Lymphocytes metabolism
B-Lymphocytes pathology
Biomarkers
Cell Plasticity
Cell Self Renewal
Drug Resistance, Neoplasm
Genetic Variation
Humans
Multiple Myeloma drug therapy
Multiple Myeloma pathology
Neoplastic Stem Cells drug effects
Neoplastic Stem Cells pathology
Phenotype
Multiple Myeloma etiology
Multiple Myeloma metabolism
Neoplastic Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 101
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 27903712
- Full Text :
- https://doi.org/10.3324/haematol.2015.138826