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Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis

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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; Waldhueter, Nils; Fleischer-Notter, Helga; Christen, Friederike; Schmitt, Clemens A; Dörken, Bernd; Pelzer, Uwe; Sinn, Marianne; Zemojtel, Tomasz; Ogawa, Seishi; Märdian, Sven; Schreiber, Adrian; Kunitz, Annegret; Krüger, Ulrike; Bullinger, Lars; Mylonas, Elena; Frick, Mareike; Damm, Frederik.

in: LEUKEMIA, Jahrgang 32, Nr. 9, 09.2018, S. 1908-1919.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Arends, CM, Galan-Sousa, J, Hoyer, K, Chan, W, Jäger, M, Yoshida, K, Seemann, R, Noerenberg, D, Waldhueter, N, Fleischer-Notter, H, Christen, F, Schmitt, CA, 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 2018, 'Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis', LEUKEMIA, Jg. 32, Nr. 9, S. 1908-1919. https://doi.org/10.1038/s41375-018-0047-7

APA

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., ... Damm, F. (2018). Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis. LEUKEMIA, 32(9), 1908-1919. https://doi.org/10.1038/s41375-018-0047-7

Vancouver

Arends CM, Galan-Sousa J, Hoyer K, Chan W, Jäger M, Yoshida K et al. Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis. LEUKEMIA. 2018 Sep;32(9):1908-1919. https://doi.org/10.1038/s41375-018-0047-7

Bibtex

@article{65b912f80625448fb78effad794ff386,
title = "Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis",
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.",
keywords = "Age Factors, Aged, Aged, 80 and over, Alleles, Biomarkers, Cell Differentiation, Clonal Evolution, DNA Mutational Analysis, Female, Gene Frequency, Hematopoiesis, Hematopoietic Stem Cells/cytology, Humans, Immunophenotyping, Male, Middle Aged, Mutation, Polymorphism, Single Nucleotide",
author = "Arends, {Christopher Maximilian} and Joel Galan-Sousa and Kaja Hoyer and Willy Chan and Marten J{\"a}ger and Kenichi Yoshida and Ricarda Seemann and Daniel Noerenberg and Nils Waldhueter and Helga Fleischer-Notter and Friederike Christen and Schmitt, {Clemens A} and Bernd D{\"o}rken and Uwe Pelzer and Marianne Sinn and Tomasz Zemojtel and Seishi Ogawa and Sven M{\"a}rdian and Adrian Schreiber and Annegret Kunitz and Ulrike Kr{\"u}ger and Lars Bullinger and Elena Mylonas and Mareike Frick and Frederik Damm",
year = "2018",
month = sep,
doi = "10.1038/s41375-018-0047-7",
language = "English",
volume = "32",
pages = "1908--1919",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "9",

}

RIS

TY - JOUR

T1 - Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis

AU - Arends, Christopher Maximilian

AU - Galan-Sousa, Joel

AU - Hoyer, Kaja

AU - Chan, Willy

AU - Jäger, Marten

AU - Yoshida, Kenichi

AU - Seemann, Ricarda

AU - Noerenberg, Daniel

AU - Waldhueter, Nils

AU - Fleischer-Notter, Helga

AU - Christen, Friederike

AU - Schmitt, Clemens A

AU - Dörken, Bernd

AU - Pelzer, Uwe

AU - Sinn, Marianne

AU - Zemojtel, Tomasz

AU - Ogawa, Seishi

AU - Märdian, Sven

AU - Schreiber, Adrian

AU - Kunitz, Annegret

AU - Krüger, Ulrike

AU - Bullinger, Lars

AU - Mylonas, Elena

AU - Frick, Mareike

AU - Damm, Frederik

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Biomarkers

KW - Cell Differentiation

KW - Clonal Evolution

KW - DNA Mutational Analysis

KW - Female

KW - Gene Frequency

KW - Hematopoiesis

KW - Hematopoietic Stem Cells/cytology

KW - Humans

KW - Immunophenotyping

KW - Male

KW - Middle Aged

KW - Mutation

KW - Polymorphism, Single Nucleotide

U2 - 10.1038/s41375-018-0047-7

DO - 10.1038/s41375-018-0047-7

M3 - SCORING: Journal article

C2 - 29491455

VL - 32

SP - 1908

EP - 1919

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 9

ER -