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

Haebe, Sarah; Keay, William; Alig, Stefan; Mohr, Anne-Wiebe; Martin, Larissa K.; Heide, Michael; Secci, Ramona; Krebs, Stefan; Blum, Helmut; Moosmann, Andreas; Louissaint, Abner; Weinstock, David M.; Thoene, Silvia; Bergwelt-Baildon, Michael von; Ruland, Jürgen; Bararia, Deepak und Weigert, Oliver (2021): The molecular ontogeny of follicular lymphoma: gene mutations succeeding the BCL2 translocation define common precursor cells. In: British Journal of Haematology, Bd. 196, Nr. 6: S. 1381-1387

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0007-1048
• Sprache: Englisch