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Spatial Mapping of Hematopoietic Clones in Human Bone Marrow.
Young, Andrew L; Davis, Hannah C; Cox, Maggie J; Parsons, Tyler M; Burkart, Samantha C; Bender, Diane E; Sun, Lulu; Oh, Stephen T; Challen, Grant A.
Afiliación
  • Young AL; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
  • Davis HC; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
  • Cox MJ; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
  • Parsons TM; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
  • Burkart SC; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
  • Bender DE; The Bursky Center for Human Immunology and Immunotherapy Programs Immunomonitoring Laboratory, Washington University School of Medicine, St. Louis, Missouri.
  • Sun L; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
  • Oh ST; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
  • Challen GA; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Blood Cancer Discov ; 5(3): 153-163, 2024 May 01.
Article en En | MEDLINE | ID: mdl-38421682
ABSTRACT
Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., >2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution of somatic mutations in the hematopoietic compartment, the restriction of somatic mutations to specific subpopulations of hematopoietic cells, and spatial constraints of these clones in the bone marrow. This proof of principle paves the way to answering fundamental questions regarding CH spatial organization and factors driving CH expansion and malignant transformation in the bone marrow.

SIGNIFICANCE:

CH occurs commonly in humans and can predispose to hematologic malignancy. Although well characterized in blood, it is poorly understood how clones are spatially distributed in the bone marrow. To answer this, we developed methods for spatially aware somatic mutation profiling to describe clonal heterogeneity in human bone marrow. See related commentary by Austin and Aifantis, p. 139.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Médula Ósea / Hematopoyesis Clonal / Mutación Límite: Humans Idioma: En Revista: Blood Cancer Discov Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Médula Ósea / Hematopoyesis Clonal / Mutación Límite: Humans Idioma: En Revista: Blood Cancer Discov Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos