Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA
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Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA. / Oberle, Anna; Brandt, Anna; Voigtländer, Minna; Thiele, Benjamin; Radloff, Janina; Schulenkorf, Anita; Alawi, Malik; Akyüz, Nuray; März, Manuela; Ford, Christopher T; Krohn-Grimberghe, Artus; Binder, Mascha.
in: HAEMATOLOGICA, Jahrgang 102, Nr. 6, 06.2017, S. 1105-1111.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA
AU - Oberle, Anna
AU - Brandt, Anna
AU - Voigtländer, Minna
AU - Thiele, Benjamin
AU - Radloff, Janina
AU - Schulenkorf, Anita
AU - Alawi, Malik
AU - Akyüz, Nuray
AU - März, Manuela
AU - Ford, Christopher T
AU - Krohn-Grimberghe, Artus
AU - Binder, Mascha
N1 - Copyright © 2017, Ferrata Storti Foundation.
PY - 2017/6
Y1 - 2017/6
N2 - Recent studies suggest that circulating tumor cells and cell-free DNA may represent powerful non-invasive tools for disease monitoring in patients with solid and hematological malignancies. Here, we conducted a pilot study in 27 myeloma patients to explore the clonotypic V(D)J rearrangement for monitoring of circulating myeloma cells (cmc-V(D)J) and cell-free myeloma DNA (cfm-V(D)J). Next-generation sequencing was used to define the myeloma V(D)J rearrangement and for subsequent peripheral blood tracking after treatment initiation. Positivity for cmc-/cfm-V(D)J was associated with conventional remission status (p<0.001) and 91% of non-responders/progressors versus 41% of responders had evidence of persistent cmc-/cfm-V(D)J (p<0.001). About half of the partial responders showed complete clearance of cmc-/cfm-V(D)J despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover and therefore decline more rapidly after initiation of effective treatment. Positivity for cmc- and cfm-V(D)J was associated with each other (p=0.042), but in 30% discordant. This indicated that cfm-V(D)J may not be generated entirely by circulating myeloma cells and may reflect overall tumor burden. Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma.
AB - Recent studies suggest that circulating tumor cells and cell-free DNA may represent powerful non-invasive tools for disease monitoring in patients with solid and hematological malignancies. Here, we conducted a pilot study in 27 myeloma patients to explore the clonotypic V(D)J rearrangement for monitoring of circulating myeloma cells (cmc-V(D)J) and cell-free myeloma DNA (cfm-V(D)J). Next-generation sequencing was used to define the myeloma V(D)J rearrangement and for subsequent peripheral blood tracking after treatment initiation. Positivity for cmc-/cfm-V(D)J was associated with conventional remission status (p<0.001) and 91% of non-responders/progressors versus 41% of responders had evidence of persistent cmc-/cfm-V(D)J (p<0.001). About half of the partial responders showed complete clearance of cmc-/cfm-V(D)J despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover and therefore decline more rapidly after initiation of effective treatment. Positivity for cmc- and cfm-V(D)J was associated with each other (p=0.042), but in 30% discordant. This indicated that cfm-V(D)J may not be generated entirely by circulating myeloma cells and may reflect overall tumor burden. Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma.
U2 - 10.3324/haematol.2016.161414
DO - 10.3324/haematol.2016.161414
M3 - SCORING: Journal article
C2 - 28183851
VL - 102
SP - 1105
EP - 1111
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
SN - 0390-6078
IS - 6
ER -