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

Dmitry Klokov (1) , Kimberly Applegate (2) , Christophe Badie (3) , Dag Anders Brede (4) , Fieke Dekkers (3) , Melis Karabulutoglu (3) , Yevgeniya Le (5) , Eric Andreas Rutten (6) , Katalin Lumniczky (7) , Maria Gomolka (8)

1 IRSN/PSE-SANTE/SESANE/LRTOX - Laboratoire de radiotoxicologie et radiobiologie expérimentale
2 University of Kentucky College of Medicine
3 Public Health England [London]
4 CERAD - Centre for Environmental Radioactivity
5 Canadian Nuclear Laboratories
6 Centre for Radiation, Chemical and Environmental Hazards
7 National Research Institute for Radiobiology & Radiohygiene
8 BfS - Bundesamt für Strahlenschutz - Federal Office for Radiation Protection

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 (aopwiki.org). 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.

Mots clés: Leukemia; ionizing radiation; acute myeloid leukemia; AML; radiationinduced leukemia; adverse outcome pathway; key event; low-dose radiation; molecular initiating event; radiation protection; risk assessment

Domaines: Sciences du Vivant [q-bio]

Dmitry Klokov, Kimberly Applegate, Christophe Badie, Dag Anders Brede, Fieke Dekkers, et al.. International expert group collaboration for developing an adverse outcome pathway for radiation induced leukemia. International Journal of Radiation Biology, 2022, 98 (12), pp.1802 - 1815. ⟨10.1080/09553002.2022.2117873⟩. ⟨irsn-04021149⟩