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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

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  • Medientyp: E-Artikel
  • Titel: Compartment-specific mutational landscape of clonal hematopoiesis
  • Beteiligte: 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; [...]
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Leukemia
  • Sprache: Englisch
  • DOI: 10.1038/s41375-022-01700-3
  • ISSN: 0887-6924; 1476-5551
  • Schlagwörter: Oncology ; Cancer Research ; Hematology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Clonal 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 (<jats:italic>n</jats:italic> = 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 <jats:italic>ASXL1</jats:italic>-mutant clones in one anatomical location but not the contralateral side, indicating intra-patient spatial heterogeneity. Analyses of lineage involvement in <jats:italic>ASXL1</jats:italic>-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 <jats:italic>ASXL1</jats:italic> 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 <jats:italic>DNMT3A</jats:italic> codon R882 variants. Collectively, our data provide novel insights into the genetics, evolution, and spatial and lineage-specific BM involvement of CH.</jats:p>