Next-generation sequencing of peripheral B-lineage cells pinpoints the circulating clonotypic cell pool in multiple myeloma
The identity of the proliferative compartment of myeloma progenitor cells remains a matter of debate. Polymerase chain reaction-based studies suggested pre-switch “clonotypic” B cells sharing the immunoglobulin (Ig) rearrangement of the malignant plasma cell (M-PC), to circulate in the blood and pos...
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Veröffentlicht in: | Blood 2014-06, Vol.123 (23), p.3618-3621 |
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Zusammenfassung: | The identity of the proliferative compartment of myeloma progenitor cells remains a matter of debate. Polymerase chain reaction-based studies suggested pre-switch “clonotypic” B cells sharing the immunoglobulin (Ig) rearrangement of the malignant plasma cell (M-PC), to circulate in the blood and possess stem cell-like properties. Here, we disprove this hypothesis. We screened peripheral blood IgM, IgG, and IgA repertoires of myeloma patients for the clonotypic rearrangement by next-generation sequencing. None of 12 cases showed pre-switch clonotypic transcripts. In the post-switch IgG/IgA repertoires, however, the clonotypic rearrangement was detected at high frequency in 6 of 8 patients with active disease, whereas it was undetectable after treatment, correlating with flow cytometric presence or absence of circulating M-PCs. Minor subclones with alternative post-switch isotypes suggested ongoing switch events and clonal evolution at the M-PC level. Our findings consistently show an absence of pre-switch clonotypic B cells, while M-PCs circulate in the peripheral blood and may contribute to spreading of the disease.
•Clonotypic B cells, long suspected to represent circulating stem-like cells, are consistently absent in the blood of myeloma patients.•Malignant plasma cells frequently circulate in the peripheral blood, show evidence for clonal evolution, and may spread the disease. |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2014-02-556746 |