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Klonale Hämatopoese und solide Neoplasien

Clonal hematopoiesis and solid neoplasms

  • Schwerpunkt: Klonale Hämatopoese
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Zusammenfassung

Hintergrund

Klonale Hämatopoese (CH) ist ein im Alter häufig auftretender prämaligner Zustand des hämatopoetischen Systems, der mit einem erhöhten kardiovaskulären Risiko und einer erhöhten Gesamtsterblichkeit einhergeht.

Fragestellung

Prävalenz und klinische Implikationen der CH bei PatientInnen mit soliden Neoplasien.

Material und Methoden

Sichtung, Zusammenfassung und Diskussion der Literatur.

Ergebnisse

CH tritt bei etwa 20–30 % der PatientInnen mit soliden Neoplasien auf. CH-Mutationen können bei der molekulargenetischen Analyse von Tumormaterial oder zellfreier DNA aus Plasma als Tumormutationen missinterpretiert werden. CH und insbesondere Mutationen in Genen der DNA-Reparatur-Maschinerie sind unter Chemo‑, Strahlen- und Poly-(Adenosindiphosphat-Ribose)-Polymerase-Inhibitor-Therapie mit einem erhöhten Risiko therapieassoziierter myeloischer Neoplasien (t-MN) assoziiert.

Schlussfolgerung

CH ist ein häufiges Phänomen bei PatientInnen mit soliden Neoplasien und hat aufgrund des t‑MN-Risikos eine hohe klinische Relevanz. Weitere Studien sind notwendig, um die Rolle der CH in diesem Patientenkollektiv besser zu verstehen und um evidenzbasierte Handlungsempfehlungen ableiten zu können.

Abstract

Background

Clonal hematopoiesis (CH) is a premalignant state of the hematopoietic system that frequently occurs in old age and is associated with an elevated cardiovascular risk and higher overall mortality.

Aim

The prevalence and clinical implications of CH in patients with solid neoplasms were examined.

Material and methods

A review, summary and discussion of the recent literature was carried out.

Results

CH occurs in 20–30% of patients with solid neoplasms. In the molecular diagnostics of tumor or cell-free DNA from plasma, CH mutations can be falsely interpreted as tumor mutations. CH and in particular mutations in the genes of the DNA damage repair machinery are associated with a higher risk of therapy-associated myeloid neoplasms (t-MN) following chemotherapy, radiotherapy and poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor therapy.

Conclusion

CH is a frequent phenomenon in patients with solid neoplasms. It has high clinical relevance due to the associated risk of t‑MN. More research is needed for a better understanding of the role of CH in this patient collective and to derive evidence-based recommendations for action.

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Abbreviations

AML:

Akute myeloische Leukämie

CCUS:

„Clonal cytopenia of undetermined significance“

cfDNA:

„cell-free DNA“ (zellfreie DNA)

CH:

„Clonal hematopoiesis“ (klonale Hämatopoese)

CHIP:

„Clonal hematopoiesis of indeterminate potential“ (klonale Hämatopoese von unbestimmtem Potenzial)

CH-PD:

„Clonal hematopoiesis with presumptive driver mutations“ (klonale Hämatopoese mit vermuteten Treibermutationen)

DDR:

„DNA damage repair“ (DNA-Reparatur)

DTA-CH:

Klonale Hämatopoese mit Nachweis einer Mutation in den Genen DNMT3A, TET2 oder ASXL1

HRD:

Defizienz der homologen Rekombination

MDS:

Myelodysplastisches Syndrom

MGUS:

Monoklonale Gammopathie unklarer Signifikanz

PARP:

Poly-(Adenosindiphosphat-Ribose)-Polymerase

t‑AML:

Therapieassoziierte akute myeloische Leukämie

t‑MDS:

Therapieassoziiertes myelodysplastisches Syndrom

t‑MN:

Therapieassoziierte myeloische Neoplasie

VAF:

Variantenallelfrequenz

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Authors and Affiliations

  1. Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland

    Christopher Maximilian Arends &  Frederik Damm

  2. Deutsches Konsortium für Translationale Krebsforschung (DKTK), Heidelberg, Deutschland

    Frederik Damm

  3. Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland

    Frederik Damm

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  1. Christopher Maximilian Arends
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Correspondence to Frederik Damm.

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Interessenkonflikt

F. Damm gibt an, Honorare und/oder Vergütungen von den Firmen AbbVie, AstraZeneca, Gilead, Incyte, Novartis und Roche erhalten zu haben. C.M. Arends gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Michael Hallek, Köln

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Arends, C.M., Damm, F. Klonale Hämatopoese und solide Neoplasien. Innere Medizin 63, 1133–1140 (2022). https://doi.org/10.1007/s00108-022-01404-x

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