Academic Journal

Tyrosine Kinase Inhibitors Play an Antiviral Action in Patients Affected by Chronic Myeloid Leukemia: A Possible Model Supporting Their Use in the Fight Against SARS-CoV-2

التفاصيل البيبلوغرافية
العنوان: Tyrosine Kinase Inhibitors Play an Antiviral Action in Patients Affected by Chronic Myeloid Leukemia: A Possible Model Supporting Their Use in the Fight Against SARS-CoV-2
المؤلفون: Galimberti S., Petrini M., Barate C., Ricci F., Balducci S., Grassi S., Guerrini F., Ciabatti E., Mechelli S., Di Paolo A., Baldini C., Baglietto L., Macera L., Spezia P. G., Maggi F.
المساهمون: Galimberti, S., Petrini, M., Barate, C., Ricci, F., Balducci, S., Grassi, S., Guerrini, F., Ciabatti, E., Mechelli, S., Di Paolo, A., Baldini, C., Baglietto, L., Macera, L., Spezia, P. G., Maggi, F.
سنة النشر: 2020
المجموعة: ARPI - Archivio della Ricerca dell'Università di Pisa
مصطلحات موضوعية: CML, COVID-19, imatinib, immunity, NanoString, nilotinib, TKI, TTV
الوصف: SARS-CoV-2 is the viral agent responsible for the pandemic that in the first months of 2020 caused about 400,000 deaths. Among compounds proposed to fight the SARS-CoV-2-related disease (COVID-19), tyrosine kinase inhibitors (TKIs), already effective in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML), have been proposed on the basis of their antiviral action already demonstrated against SARS-CoV-1. Very few cases of COVID-19 have been reported in Ph+ ALL and in CML Italian cohorts; authors suggested that this low rate of infections might depend on the use of TKIs, but the biological causes of this phenomenon remain unknown. In this study, the CML model was used to test if TKIs would sustain or not the viral replication and if they could damage patient immunity. Firstly, the infection and replication rate of torquetenovirus (TTV), whose load is inversely proportional to the host immunological control, have been measured in CML patients receiving nilotinib. A very low percentage of subjects were infected at baseline, and TTV did not replicate or at least showed a low replication rate during the follow-up, with a mean load comparable to the measured one in healthy subjects. Then, after gene expression profiling experiments, we found that several “antiviral” genes, such as CD28 and IFN gamma, were upregulated, while genes with “proviral” action, such as ARG-1, CEACAM1, and FUT4, were less expressed during treatment with imatinib, thus demonstrating that TKIs are not detrimental from the immunological point of view. To sum up, our data could offer some biological explanations to the low COVID-19 occurrence in Ph+ ALL and CML patients and sustain the use of TKIs in COVID-19, as already proposed by several international ongoing studies.
نوع الوثيقة: article in journal/newspaper
وصف الملف: ELETTRONICO
اللغة: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/33014780; info:eu-repo/semantics/altIdentifier/wos/WOS:000570446700001; volume:10; numberofpages:9; journal:FRONTIERS IN ONCOLOGY; https://hdl.handle.net/11568/1054080; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85091031111
DOI: 10.3389/fonc.2020.01428
الاتاحة: https://hdl.handle.net/11568/1054080
https://doi.org/10.3389/fonc.2020.01428
Rights: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.B00DA4A7
قاعدة البيانات: BASE