Cordycepin (3'dA) Induces Cell Death of AC133+ Leukemia Cells via Re-Expression of WIF1 and Down-Modulation of MYC.

Wnt/ß-catenin signaling is critically required for the development and maintenance of leukemia stem cells (LSCs) in acute myeloid leukemia (AML) by constitutive activation of myeloid regeneration-related pathways. Cell-intrinsic activation of canonical Wnt signaling propagates in the nucleus by ß-catenin translocation, where it induces expression of target oncogenes such as JUN, MYC and CCND1. As the Wnt/ß-catenin pathway is now well established to be a key oncogenic signaling pathway promoting leukemic myelopoiesis, targeting it would be an effective strategy to impair LSC functionality. Although the effects of the adenosine analogue cordycepin in repressing ß-catenins and destabilizing the LSC niche have been highlighted, the cellular and molecular effects on AML-LSC have not been fully clarified. In the present study, we evaluated the potency and efficacy of cordycepin, a selective repressor of Wnt/ß-catenin signaling with anti-leukemia properties, on the AC133+ LSC fraction. Cordycepin effectively reduces cell viability of the AC133+ LSCs in the MUTZ-2 cell model and patient-derived cells through the induction of apoptosis. By Wnt-targeted RNA sequencing panel, we highlighted the re-expression of WIF1 and DKK1 among others, and the consequent downregulation of MYC and PROM1 (CD133) following MUTZ-2 cell exposure to increasing doses of cordycepin. Our results provide new insights into the molecular circuits involved in pharmacological inhibition mediated by cordycepin reinforcing the potential of targeting the Wnt/ß-catenin and co-regulatory complexes in AML.

Seroprevalence of SARS-CoV2 in IBD Patients Treated with Biologic Therapy.

BACKGROUND AND AIMS: A similar course of COVID-19 in patients with inflammatory bowel diseases [IBD] and in the general population has been reported. However, disease prevalence in IBD patients is presently unknown. In this prospective observational study, we aimed at determining SARS-CoV2 infection prevalence in IBD patients treated with biologic therapy. METHODS: From IBD patients under biologic therapy and recruited from three different locations in Italy and Germany, 354 sera were evaluated for antibody presence by RBD ELISA. Control groups were: i] age-matched healthy subjects tested in the same time period in Milan, Italy; ii] healthy subjects collected in the pre-COVID era; iii] IBD patients under biologic therapy collected in the pre-COVID era. RESULTS: Eight out of 354 patients tested positive for the anti-RBD-SARS-CoV2 IgG antibody [prevalence 2.3%]. The percentage of IgG-positive patients among those recruited from Milan was significantly higher than among those recruited from other locations [prevalence 5.4% vs 0.4%, p <0.005]. IgG-positive patients reported a significantly higher incidence of fever, anosmia, and ageusia, and were more likely to have entered into close contact with COVID-19-positive subjects before the study enrolment. CONCLUSIONS: Seroprevalence of SARS-CoV2 in IBD patients treated with biologic therapy reflects values measured in the local general population. Specific symptoms and contact history with SARS-CoV2-infected individuals strongly increase the likelihood of SARS-CoV2 seropositivity.