Next-generation sequencing of peripheral B-lineage cells pinpoints the circulating clonotypic cell pool in multiple myeloma

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Next-generation sequencing of peripheral B-lineage cells pinpoints the circulating clonotypic cell pool in multiple myeloma. / Thiele, Benjamin; Kloster, Marie; Alawi, Malik; Indenbirken, Daniela; Trepel, Martin; Grundhoff, Adam; Binder, Mascha.

in: BLOOD, Jahrgang 123, Nr. 23, 05.06.2014, S. 3618-21.

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@article{07d5e4f5eb5a43a3b24d30235635d9d2,
title = "Next-generation sequencing of peripheral B-lineage cells pinpoints the circulating clonotypic cell pool in multiple myeloma",
abstract = "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.",
author = "Benjamin Thiele and Marie Kloster and Malik Alawi and Daniela Indenbirken and Martin Trepel and Adam Grundhoff and Mascha Binder",
note = "{\textcopyright} 2014 by The American Society of Hematology.",
year = "2014",
month = jun,
day = "5",
doi = "10.1182/blood-2014-02-556746",
language = "English",
volume = "123",
pages = "3618--21",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "23",

}

RIS

TY - JOUR

T1 - Next-generation sequencing of peripheral B-lineage cells pinpoints the circulating clonotypic cell pool in multiple myeloma

AU - Thiele, Benjamin

AU - Kloster, Marie

AU - Alawi, Malik

AU - Indenbirken, Daniela

AU - Trepel, Martin

AU - Grundhoff, Adam

AU - Binder, Mascha

N1 - © 2014 by The American Society of Hematology.

PY - 2014/6/5

Y1 - 2014/6/5

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2014-02-556746

DO - 10.1182/blood-2014-02-556746

M3 - SCORING: Journal article

C2 - 24753536

VL - 123

SP - 3618

EP - 3621

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 23

ER -