Cited by 195Acute Myeloid Leukemia ResearchCancer Genomics and DiagnosticsHematopoietic Stem Cell Transplantation

Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis

Arends, Christopher Maximilian, Galan-Sousa, Joel, Hoyer, Kaja, Chan, Willy, Jäger, Marten, Yoshida, Kenichi, Seemann, Ricarda, Noerenberg, Daniel +17 more·2018·Leukemia

Abstract

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 < .001). Cancer patients with a clonal mutation other than DNMT3A required more often red blood cell transfusions and dose reductions. Our results provide novel insights into cellular distribution of clonal mutations, their dynamics under chemotherapy, and advocate for systematic analyses for CHIP in cancer patients.

Integrity signals

Registry

Crossref · 10.1038/s41375-018-0047-7

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

1 of the 50 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Arends, C. M., Galan-Sousa, J., Hoyer, K., Chan, W., Jäger, M., Yoshida, K., Seemann, R., Noerenberg, D., Waldhueter, N., Fleischer-Notter, H., Christen, F., Schmitt, C. A., Dörken, B., Pelzer, U., Sinn, M., Zemojtel, T., Ogawa, S., Märdian, S., Schreiber, A., Kunitz, A., Krüger, U., Bullinger, L., Mylonas, E., Frick, M., & Damm, F.
Affiliations
  • Humboldt-Universität zu Berlin (DE)
  • Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
  • Kyoto University (JP)
  • Max Delbrück Center (DE)
Venue
Leukemia
Published
2018-03-01
Volume
32
Issue
9
Pages
1908-1919
ISSN
  • 0887-6924 (ISSN-L)
  • 1476-5551
OpenAlex
W2789900003
Cited by
194
References
50
Citations by year
2026: 9 · 2025: 20 · 2024: 25 · 2023: 26 · 2022: 31 · 2021: 30 · 2020: 20 · 2019: 27 · 2018: 6
FWCI
14.88
Type
journal article
Language
en
Open access
closed
Locations
  • Leukemia (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
clonal hematopoiesis of indeterminate potential, clonal hematopoiesis, variant allele frequency, DNMT3A, hematopoietic stem cells, chemotherapy, hematologic cancer, red blood cell transfusion
MeSH terms
Age Factors, Aged, Aged, 80 and over, Alleles, Cell Differentiation, DNA Mutational Analysis, Female, Gene Frequency, Hematopoiesis, Hematopoietic Stem Cells, Humans, Male, Middle Aged, Mutation, Biomarkers, Immunophenotyping, Polymorphism, Single Nucleotide, Clonal Evolution

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review