International expert group collaboration for developing an adverse outcome pathway for radiation induced leukemia

Dmitry Klokov*, Kimberly Applegate, Christophe Badie, Dag Anders Brede, Fieke Dekkers, Melis Karabulutoglu, Yevgeniya Le, Eric Andreas Rutten, Katalin Lumniczky, Maria Gomolka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Purpose: The concept of the adverse outcome pathway (AOP) has recently gained significant attention as to its potential for incorporation of mechanistic biological information into the assessment of adverse health outcomes following ionizing radiation (IR) exposure. This work is an account of the activities of an international expert group formed specifically to develop an AOP for IR-induced leukemia. Group discussions were held during dedicated sessions at the international AOP workshop jointly organized by the MELODI (Multidisciplinary European Low Dose Initiative) and the ALLIANCE (European Radioecology Alliance) associations to consolidate knowledge into a number of biological key events causally linked by key event relationships and connecting a molecular initiating event with the adverse outcome. Further knowledge review to generate a weight of evidence support for the Key Event Relationships (KERs) was undertaken using a systematic review approach. Conclusions: An AOP for IR-induced acute myeloid leukemia was proposed and submitted for review to the OECD-curated AOP-wiki ( The systematic review identified over 500 studies that link IR, as a stressor, to leukemia, as an adverse outcome. Knowledge gap identification, although requiring a substantial effort via systematic review of literature, appears to be one of the major added values of the AOP concept. Further work, both within this leukemia AOP working group and other similar working groups, is warranted and is anticipated to produce highly demanded products for the radiation protection research community.

Original languageEnglish
Pages (from-to)1802-1815
Number of pages14
JournalInternational Journal of Radiation Biology
Issue number12
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s). Published with license by Taylor and Francis Group, LLC.


  • AML
  • Leukemia
  • acute myeloid leukemia
  • adverse outcome pathway
  • ionizing radiation
  • key event
  • low-dose radiation
  • molecular initiating event
  • radiation protection
  • radiation-induced leukemia
  • risk assessment


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