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Background: Iron overload is considered an unfavorable prognosis in myelodysplastic syndrome (MDS) even in those undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although iron chelation therapy has improved the prognosis of these patients to some extent, the effect has not yet been satisfactory., Objectives: This study aimed to investigate the impact of granulocyte colony-stimulating factor and decitabine (G-DAC)-containing conditioning in iron-overloaded MDS patients undergoing allo-HSCT., Design: This was a retrospective study., Methods: One hundred and ninety-seven patients were enrolled in this retrospective study. Based on the level of serum ferritin (SF) and conditioning regimen, all patients enrolled were divided into four groups: SF < 1000 µg/L with G-DAC conditioning (cohort 1), SF < 1000 µg/L with non-G-DAC conditioning (cohort 2), SF ⩾ 1000 µg/L with G-DAC conditioning (cohort 3), and SF ⩾ 1000 µg/L with non-G-DAC conditioning (cohort 4). The clinical features and prognosis of the four groups were analyzed., Results: Significant differences in the 2-year overall survival (OS), disease-free survival (DFS), and the cumulative incidence of non-relapse mortality (NRM) were observed between the four groups. Multivariate analysis revealed that SF ⩾ 1000 µg/L was a risk factor for OS, DFS, and NRM while G-DAC-containing conditioning was a protective factor. Intriguingly, when cohort 1 to cohort 4 were included in the multivariate analysis, only cohort 4 was a risk factor for OS, DFS, and NRM, cohort 3 had no difference in prognosis compared with patients with SF < 1000 µg/L., Conclusion: The poor prognosis of patients with iron overload may be overcome by G-DAC-containing conditioning partly., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Competing Interests: Competing interests RPG is a consultant to NexImmune Inc. Nanexa Pharma Ascentage Pharm Group and Antengene Biotech LLC, Medical Director of FFF Enterprises Inc.; Partner in AZCA Inc.; Board of Directors of Russian Foundation for Cancer Research Support and Scientific Advisory Board: StemRad Ltd. Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonization Good Clinical Practice guideline and received approval from the Ethics Committee of the First Affiliated Hospital of Jinan University (KY-2023-117) and is registered on clinicaltrials.gov (NCT05919199). Informed consent was obtained from all participants. All clinical data including PET/CT images and bone marrow samples were obtained and published after written informed consent. The experiments of PDX models were approved by the Institutional Animal Care and Use Committee of Jinan University (JNU-IACUC) and conformed to all relevant regulatory standards. Mice were kept in ventilated cages under pathogen-free conditions with 12 h light and dark cycle and given water and food ad libitum. All 18F-FDG experiments were conducted with the approvals mentioned above and with proper radiation protection.

Overexpression of Wilms' tumor ( WT1 ) is frequently observed in myelodysplastic syndrome (MDS), which has been proposed as a prognostic marker. However, the prognostic role of WT1 expression in different contexts remains to be fully elucidated. We retrospectively assessed the relationships between WT1 levels and preexisting prognostic factors to further investigate its prognostic role under different contexts. In our study, WT1 expression was positively correlated with WHO 2016 classification and IPSS-R stratification. Lower WT1 expression was found in relation to TET2 , TP53 , CD101, or SRSF2 mutations, while mutant NPM1 patients possessed higher level. Notably, WT1 overexpression maintained its inferior prognostic effect on overall survival (OS) in TP53 -wild patients but not in TP53 -mutated group. In multivariate analysis, higher WT1 expression was a risk factors for OS in EB patients without TP53 mutations. Overall, WT1 expression was useful to predict prognosis for MDS and its prognostic role was impacted by some gene mutations.

Purpose: Brusatol, a natural quassinoid that is isolated from a traditional Chinese herbal medicine known as Bruceae Fructus, possesses biological activity in various types of human cancers, but its effects in nasopharyngeal carcinoma (NPC) have not been reported. This study aimed to explore the effect and molecular mechanism of brusatol in NPC in vivo and in vitro., Methods: The antiproliferative effect of brusatol was assessed by MTT and colony formation assays. Apoptosis was determined by flow cytometry. The expression of mitochondrial apoptosis, cell cycle arrest, and Akt/mTOR pathway proteins were determined by western blot analysis. Further in vivo confirmation was performed in a nude mouse model., Results: Brusatol showed antiproliferative activity against four human NPC cell lines (CNE-1, CNE-2, 5-8F, and 6-10B) in a dose-dependent manner. This antiproliferative effect was accompanied by mitochondrial apoptosis and cell cycle arrest through the modulation of several key molecular targets, such as Bcl-xl, Bcl-2, Bad, Bax, PARP, Caspase-9, Caspase-7, Caspase-3, Cdc25c, Cyclin B1, Cdc2 p34, and Cyclin D1. In addition, we found that brusatol inhibited the activation of Akt, mTOR, 4EBP1, and S6K, suggesting that the Akt/mTOR pathway is a key underlying mechanism by which brusatol inhibits growth and promotes apoptosis. Further in vivo nude mouse models proved that brusatol significantly inhibited the growth of CNE-1 xenografts with no significant toxicity., Conclusions: These observations indicate that brusatol is a promising antitumor drug candidate or a supplement to current chemotherapeutic therapies to treat NPC.