> Details

Hartmann, Luise; Hecker, Judith S.; Rothenberg-Thurley, Maja; Rivière, Jennifer; Jentzsch, Madlen; Ksienzyk, Bianka; Buck, Michèle C.; van der Garde, Mark; Fischer, Luise; Winter, Susann; Rauner, Martina; Tsourdi, Elena; Weidner, Heike; Sockel, Katja; Schneider, Marie; Kubasch, Anne S.; Nolde, Martin; Hausmann, Dominikus; Lützner, Jörg; Goralski, Szymon; Bassermann, Florian; Spiekermann, Karsten; Hofbauer, Lorenz C.; Schwind, Sebastian; [...]

Compartment-specific mutational landscape of clonal hematopoiesis

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Compartment-specific mutational landscape of clonal hematopoiesis
  • Contributor: Hartmann, Luise; Hecker, Judith S.; Rothenberg-Thurley, Maja; Rivière, Jennifer; Jentzsch, Madlen; Ksienzyk, Bianka; Buck, Michèle C.; van der Garde, Mark; Fischer, Luise; Winter, Susann; Rauner, Martina; Tsourdi, Elena; Weidner, Heike; Sockel, Katja; Schneider, Marie; Kubasch, Anne S.; Nolde, Martin; Hausmann, Dominikus; Lützner, Jörg; Goralski, Szymon; Bassermann, Florian; Spiekermann, Karsten; Hofbauer, Lorenz C.; Schwind, Sebastian; [...]
  • Published: Springer Science and Business Media LLC, 2022
  • Published in: Leukemia, 36 (2022) 11, Seite 2647-2655
  • Language: English
  • DOI: 10.1038/s41375-022-01700-3
  • ISSN: 0887-6924; 1476-5551
  • Origination:
  • Footnote:
  • Description: AbstractClonal hematopoiesis (CH) is characterized by somatic mutations in blood cells of individuals without hematologic disease. While the mutational landscape of CH in peripheral blood (PB) has been well characterized, detailed analyses addressing its spatial and cellular distribution in the bone marrow (BM) compartment are sparse. We studied CH driver mutations in healthy individuals (n = 261) across different anatomical and cellular compartments. Variant allele frequencies were higher in BM than PB and positively correlated with the number of driver variants, yet remained stable during a median of 12 months of follow-up. In CH carriers undergoing simultaneous bilateral hip replacement, we detected ASXL1-mutant clones in one anatomical location but not the contralateral side, indicating intra-patient spatial heterogeneity. Analyses of lineage involvement in ASXL1-mutated CH showed enriched clonality in BM stem and myeloid progenitor cells, while lymphocytes were particularly involved in individuals carrying the c.1934dupG variant, indicating different ASXL1 mutations may have distinct lineage distribution patterns. Patients with overt myeloid malignancies showed higher mutation numbers and allele frequencies and a shifting mutation landscape, notably characterized by increasing prevalence of DNMT3A codon R882 variants. Collectively, our data provide novel insights into the genetics, evolution, and spatial and lineage-specific BM involvement of CH.