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Haebe, S.* ; Keay, W.* ; Alig, S.* ; Mohr, A.-W. ; Martin, L.K. ; Heide, M.* ; Secci, R.* ; Krebs, S.* ; Blum, H.* ; Moosmann, A.* ; Louissaint, A.* ; Weinstock, D.M.* ; Thoene, S.* ; von Bergwelt-Baildon, M.* ; Ruland, J.* ; Bararia, D.* ; Weigert, O.*

The molecular ontogeny of follicular lymphoma: Gene mutations succeeding the BCL2 translocation define common precursor cells.

Br. J. Haematol., DOI: 10.1111/bjh.17990 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Relapsed follicular lymphoma (FL) can arise from common progenitor cells (CPCs). Conceptually, CPC-defining mutations are somatic alterations shared by the initial and relapsed tumours, mostly B-cell leukaemia/lymphoma 2 (BCL2)/immunoglobulin heavy locus (IGH) translocations and other recurrent gene mutations. Through complementary approaches for highly sensitive mutation detection, we do not find CPC-defining mutations in highly purified BCL2/IGH-negative haematopoietic progenitor cells in clinical remission samples from three patients with relapsed FL. Instead, we find cells harbouring the same BCL2/IGH translocation but lacking CREB binding protein (CREBBP), lysine methyltransferase 2D (KMT2D) and other recurrent gene mutations. Thus, (i) the BCL2/IGH translocation can precede CPC-defining mutations in human FL, and (ii) BCL2/IGH-translocated cells can persist in clinical remission.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Lymphoma ; Molecular Ontogeny ; Common Progenitor Cells ; Bcl2 ; Igh Translocation ; Minimal Residual Disease; Stem-cell; B-cells
ISSN (print) / ISBN 0007-1048
e-ISSN 1365-2141
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Grants ProjektDEAL
Max-Eder Program of the Deutsche Krebshilfe
Dr Mildred Scheel postdoctoral fellowship of the Deutsche Krebshilfe
National Cancer Institute (NCI)
Follicular Lymphoma Foundation
European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)