Correlation of a four gene set with H-ARS severity in irradiated minipigs treated with Myelo001.

Authors

Nikolai Schmid, Aleš Tichý, Lenka Lecová, Corinna Asang, Dirk Pleimes, Samantha Stewart, Mandy Kasper, Patrick Ostheim, Stefan Eder, Matthias Port, Michael Abend

Published in

International journal of radiation biology. Pages 1-12. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

Early prediction of hematological acute radiation syndrome (H-ARS) saves lives. For H-ARS severity prediction, we established a four-gene panel (FDXR, DDB2, POU2AF1, WNT3) using leukemia patients and non-human primates. Further confirmation in 12 minipigs failed, due to a weak response of these genes after irradiation.
Here, we intended to confirm previous findings using a larger cohort (n = 19) and assess the impact of Myelo001 on clinical progression and gene expression. All minipigs received 2.1 Gy total-body irradiation (LD ≈ 40/30). The study included an irradiated control group and two irradiated groups treated with Myelo001 (11 or 15 days). Peripheral blood was collected six days before and on days 1-, 3-, and 10 after irradiation. RNA was isolated, reverse-transcribed, and analyzed by qRT-PCR using TaqMan assays. Differential gene expression (DGE) was calculated relative to pre-irradiation samples.
WNT3 was undetectable in most animals. No significant difference in gene expression, survival, or clinical progression were found between Myelo001-treated and untreated animals, so treatment groups were pooled for DGE analyses. Across all time points, no significant changes in DGE were observed, except for slight DDB2 upregulation on day 3 (DGE = 2.3). The expected pattern of upregulated (DGE >2) FDXR/DDB2 with simultaneous downregulation (DGE <0.5) of POU2AF1, was absent (except on day one in one minipig). This missing pattern contrasted with an on average 5.5-fold reduction in lymphocyte counts, indicative of severe H-ARS. Also, no age or sex related changes were observed.
This independent minipig study confirms previous work showing that these genes do not exhibit statistically significant radiation-responsiveness in this animal model. Under the experimental conditions applied, no significant age or sex related changes nor treatment-related effects of Myelo001 were observed, which may reflect model-specific limitations or a lack of efficacy in this setting, or a combination of both.

PMID:
42566227
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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