Contamination of seven workers with

Widespread contamination occurred in the building in which radiation waste was handled. An occurrence of internal contamination of workers was also suspected. Therefore, workers were measured in vivo and bioassay was performed too. Estimation of committed effective dose had to be based on results of excretion analysis as irremovable surface contamination occurred on the skin and hair of workers, thus influencing results of in vivo measurements. The results of bioassay of 7 workers are presented. Intakes and committed effective doses were calculated from excretion data using IMBA Professional Plus software. The best fits for the most of workers were obtained when combination of acute and chronic intakes was used. Acute intakes varied from 135 Bq to 1300 Bq, chronic intakes from 0.03 Bq/d to 0.3 Bq/d. Committed effective doses from 3 to 36 mSv were estimated for individual workers

Super-enhancer-based identification of a BATF3/IL-2R-module reveals vulnerabilities in anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises systemic anaplastic lymphoma kinase (ALK)-positive, and ALK-negative, primary cutaneous and breast implant-associated ALCL. Prognosis of some ALCL subgroups is still unsatisfactory, and already in second line effective treatment options are lacking. To identify genes defining ALCL cell state and dependencies, we here characterize super-enhancer regions by genome-wide H3K27ac ChIP-seq. In addition to known ALCL key regulators, the AP-1-member BATF3 and IL-2 receptor (IL2R)-components are among the top hits. Specific and high-level IL2R expression in ALCL correlates with BATF3 expression. Confirming a regulatory link, IL-2R-expression decreases following BATF3 knockout, and BATF3 is recruited to IL2R regulatory regions. Functionally, IL-2, IL-15 and Neo-2/15, a hyper-stable IL-2/IL-15 mimic, accelerate ALCL growth and activate STAT1, STAT5 and ERK1/2. In line, strong IL-2Rα-expression in ALCL patients is linked to more aggressive clinical presentation. Finally, an IL-2Rα-targeting antibody-drug conjugate efficiently kills ALCL cells in vitro and in vivo. Our results highlight the importance of the BATF3/IL-2R-module for ALCL biology and identify IL-2Rα-targeting as a promising treatment strategy for ALCL