Universität zu Köln

Paschold, Lisa, Willscher, Edith, Bein, Julia, Vornanen, Martine, Eichenauer, Dennis A., Simnica, Donjete, Thiele, Benjamin ORCID: 0000-0002-4096-3309, Wickenhauser, Claudia, Rosenwald, Andreas, Bernd, Heinz-Wolfram, Klapper, Wolfram, Feller, Alfred C., Ott, German, Fend, Falko, Hartmann, Sylvia and Binder, Mascha ORCID: 0000-0003-0663-3004 (2021). Evolutionary clonal trajectories in nodular lymphocyte-predominant Hodgkin lymphoma with high risk of transformation. Haematologica, 106 (10). S. 2654 - 2667. PAVIA: FERRATA STORTI FOUNDATION. ISSN 0390-6078

Full text not available from this repository.

Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Paschold, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Willscher, Edith UNSPECIFIED UNSPECIFIED UNSPECIFIED Bein, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Vornanen, Martine UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichenauer, Dennis A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Simnica, Donjete UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Benjamin UNSPECIFIED orcid.org/0000-0002-4096-3309 UNSPECIFIED Wickenhauser, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenwald, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernd, Heinz-Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Klapper, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Feller, Alfred C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ott, German UNSPECIFIED UNSPECIFIED UNSPECIFIED Fend, Falko UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Binder, Mascha UNSPECIFIED orcid.org/0000-0003-0663-3004 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-601609
DOI:	10.3324/haematol.2021.278427
Journal or Publication Title:	Haematologica
Volume:	106
Number:	10
Page Range:	S. 2654 - 2667
Date:	2021
Publisher:	FERRATA STORTI FOUNDATION
Place of Publication:	PAVIA
ISSN:	0390-6078
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LARGE-CELL LYMPHOMA; TUMOR-CELLS; PROGNOSTIC IMPACT; GERMINAL-CENTERS; H-CELLS; DISEASE; IMMUNOGLOBULIN; CLL Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60160