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Szatmári Tünde

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Lumniczky Katalin
Bone marrow-derived extracellular vesicles influence radiation-induced leukemogenesis

Aug 29 - kedd

14:40 – 15:00

Orvosi biofizika és sugárbiológia

E16

Bone marrow-derived extracellular vesicles influence radiation-induced leukemogenesis

Rita Hargitai, Tünde Szatmári, Ilona Csordás, Dávid Kis, Enikő Kis, Géza Sáfrány and Katalin Lumniczky

National Public Health Centre, Department of Radiobiology and Radiohygiene, Unit of Radiation Medicine, Budapest, Hungary

Haematological malignancies are considered the main long-term consequences of bone marrow (BM) irradiation. Ionizing radiation (IR) damages the stem and progenitor cells and alters signalling between the stem cell compartment and the BM stroma. The main objective of our work was to investigate extracellular vesicles (EVs)-mediated IR effects on leukaemogenesis after irradiation and to study possible underlying mechanisms using an in vivo murine model. Leukaemia incidence was followed in the CBA mouse model either irradiated or treated with EVs isolated from the BM supernatant of irradiated mice or subjected to both irradiation and EV treatment. Compared to spontaneous acute myeloid leukaemia (AML) incidence (below 1%), high dose (3 Gy) irradiation increased the incidence to 19%. EV treatment resulted in 4.5-6% leukaemia incidence with no significant difference between mice treated with EVs isolated from irradiated or non-irradiated animals. The combination of irradiation and EV treatment had an additive effect. Myeloid leukemias had two distinct phenotypes: a classical myeloblastic phenotype with a quick deterioration of the health status of the mice and increased bone marrow infiltration with myeloid blasts and a myelomonocytic phenotype with a slow clinical progression. EV treatment had a significant impact on leukaemia phenotype significantly increasing the frequency of the aggressive type myeloblastic leukemia. Lymphoid malignancies were also noted after irradiation and their incidence increased with the dose, though treatment of mice with EVs did not increase the incidence of this disease. In conclusion we showed that EVs influenced both the incidence and the phenotype of radiation-induced myeloid leukaemias but not of lymphoid ones. Our results also highlight the role of intercellular signalling mechanisms in radiation-induced leukemogenesis.

Funding: Euratom research and training programme 2014-2018, grant agreement No 662287 (CONCERT)