Effect of SARS-CoV-2 Entry Factors on Myeloid Cancers

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel, highly pathogenic coronavirus that has spread rapidly worldwide and caused an international public health emergency. Patients with hematological cancers are regarded as a high-risk group for coronavirus disease 2019 (COVID-19). However, few reports have investigated factors that might account for the differential severity of COVID-19 disease in these patients. Methods: Gene expression of SARS-CoV-2 entry-promoting factors and entry-restricting factors and the associated effects on myeloid malignancies were evaluated. Gene expression levels of 11 SARS-CoV-2 entry-promoting factors and 4 SARS-CoV-2 entry-restricting factors were analyzed in patients with myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), and acute myeloid leukemia and its subtypes. Results: Expression levels of promoting and restricting factors were most affected in MDS. Specifically, 4 of the 11 analyzed SARS-CoV-2 entry-promoting factors were significantly increased (TMPRSS4, CD 209, CLEC4G, and CTSB), and 2 of the 4 analyzed SARS-CoV-2 entry-restricting factors were significantly decreased (IFITM1 and IFITM2) in MDS. Patients with CML also exhibited a pattern of significant changes in SARS-CoV-2 entry-promoting and entry-restricting factors. Five of the 11 analyzed SARS-CoV-2 entry-promoting factors were significantly increased (ACE2, TMPRSS2, TMPRSS4, ANPEP, CD209), and 1 of the 4 analyzed SARS-CoV-2 entry-restricting factors was significantly decreased (LY6E) in CML. Conclusions: The present and past results highlight the importance of investigating SARS-CoV-2 entrypromoting factors and entry-restricting factors, because of their crucial role in determining the differential severity of COVID-19 disease.