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Evolutionary clonal trajectories in nodular lymphocyte-predominant Hodgkin lymphoma with high risk of transformation

Paschold, Lisa; Willscher, Edith; Bein, Julia; Vornanen, Martine; Eichenauer, Dennis A.; Simnica, Donjete; Thiele, Benjamin; Wickenhauser, Claudia; Rosenwald, Andreas; Bernd, Heinz Wolfram; Klapper, Wolfram; Feller, Alfred C.; Ott, German; Fend, Falko; Hartmann, Sylvia; Binder, Mascha (2021-10)

 
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Paschold, Lisa
Willscher, Edith
Bein, Julia
Vornanen, Martine
Eichenauer, Dennis A.
Simnica, Donjete
Thiele, Benjamin
Wickenhauser, Claudia
Rosenwald, Andreas
Bernd, Heinz Wolfram
Klapper, Wolfram
Feller, Alfred C.
Ott, German
Fend, Falko
Hartmann, Sylvia
Binder, Mascha
10 / 2021


doi:10.3324/haematol.2021.278427
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https://urn.fi/URN:NBN:fi:tuni-202111088245

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Peer reviewed
Tiivistelmä
The B-cell architecture of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is complex since it is composed of malignant lymphocyte-predominant cells along with a rich B-cell bystander environment. To gain insight into molecular determinants of disease transformation, we studied B-cell evolutionary trajectories in lymphoma tissue from diagnosis to relapse or transformation to non-Hodgkin lymphoma by next-generation sequencing of immunoglobulin heavy chains. Patients with NLPHL that later transformed were older and showed IgD negativity, absence of the characteristic IGHV3/IGHD3/IGHJ6 lymphocyte-predominant rearrangement and high repertoire clonality. We constructed phylogenetic trees within the compartment of the malignant clone to investigate clonal evolution. In all relapsing cases, the lymphocyte-predominant rearrangement was identical at diagnosis and relapse. NLPHL cases with transformation showed more complex trajectories with strong intraclonal diversification. The dominant founder clone in transformations showed clonal evolution if derived from the same cell of origin, or arose from a different cell of origin. Together, our data point to a significant role of antigenic drive in the transformation of NLHPL and identify high B-cell repertoire clonality with dominant intraclonal lymphocyte-predominant cell diversification as a hallmark of transformation. Sequencing of initial paraffin-embedded tissue may therefore be applied diagnostically to identify NLPHL cases with high risk of transformation.
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Kalevantie 5
PL 617
33014 Tampereen yliopisto
oa[@]tuni.fi | Tietosuoja | Saavutettavuusseloste
 

 

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Kalevantie 5
PL 617
33014 Tampereen yliopisto
oa[@]tuni.fi | Tietosuoja | Saavutettavuusseloste