Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis
| Autor: | Nils Waldhueter, Adrian Schreiber, Helga Fleischer-Notter, Tomasz Zemojtel, Sven Märdian, Mareike Frick, Kaja Hoyer, Marianne Sinn, Seishi Ogawa, Friederike Christen, Annegret Kunitz, Uwe Pelzer, Lars Bullinger, Frederik Damm, Ulrike Krüger, Kenichi Yoshida, Joel Galan-Sousa, Willy Chan, Daniel Noerenberg, Marten Jäger, Clemens A. Schmitt, Elena Mylonas, Bernd Dörken, Ricarda Seemann, Christopher Maximilian Arends |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cancer Research Myeloid DNA Mutational Analysis Biology medicine.disease_cause Somatic evolution in cancer Polymorphism Single Nucleotide Immunophenotyping Clonal Evolution 03 medical and health sciences 0302 clinical medicine Gene Frequency medicine Humans Peripheral blood cell Alleles Aged Aged 80 and over Mutation Age Factors Cancer Cell Differentiation Hematology Middle Aged medicine.disease Hematopoietic Stem Cells Hematopoiesis Haematopoiesis 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Female Bone marrow Biomarkers |
| Zdroj: | Leukemia. 32(9) |
| ISSN: | 1476-5551 |
| Popis: | Clonal hematopoiesis of indeterminate potential (CHIP) occurs in an age-related manner and associates with an increased risk of hematologic cancer, atherosclerotic disease, and shorter overall survival. Little is known about the cell of origin, repartition patterns of clonal mutations within the hematopoietic differentiation tree, and its dynamics under evolutionary pressure. Using targeted sequencing, CHIP was identified in 121 out of 437 elderly individuals (27.7%). Variant allele frequencies (VAFs) of 91 mutations were studied in six peripheral blood cell fractions. VAFs were significantly higher in monocytes, granulocytes, and NK-cells compared to B- or T cells. In all cases with available bone marrow material, mutations could be identified in Lin−CD34+CD38− HSCs with subsequent expansion to myeloid primed progenitors. In 22 patients with solid cancer receiving (radio-)chemotherapy, longitudinal study of 32 mutations at 121 time points identified relative VAF changes of at least 50% in 13/32 mutations. VAFs of DNMT3A, were stable in 12/13 cases (P |
| Databáze: | OpenAIRE |
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