Aberrant expression of Human Endogenous Retrovirus K9-derived elements is associated with better clinical outcome of acute myelocytic leukemia

Author:

Yanagiya Ryo1,Nakagawa So1,Onizuka Makoto1,Kotani Ai2

Affiliation:

1. Tokai University

2. Osaka University

Abstract

Abstract

Background: Acute myelocytic leukemia (AML) is a common hematological malignancy in adults. Although several risk stratifications based on cytogenetic and molecular abnormalities are available to decide the indication of allogeneic hematopoietic cell transplantation (allo-HCT), planning treatment strategies for AML without them remains challenging. Using transcriptome datasets, we investigated the association of event-free survival (EFS) of intensively treated AML cases and the aberrant expression status of endogenous retrovirus (ERV)-derived open reading frames (ORFs), which have been reported to be associated with the pathophysiology of various malignancies and have the potential to become neoantigens in specific cancers. Results: The expression values of human ERV family K9 (HERVK9) ORFs were found to be associated with EFS, independent of conventional risk stratifications. Furthermore, it was revealed that AML cells with higher expression of HERVK9 activated antigen processing and presentation, accompanied by excess expression of genes associated with responses to adaptive immune reaction and apoptosis, indicating that aberrant expression of HERVK9 may initiate an antineoplastic immune response against themselves via excess antigen presentation. Conclusions: In summary, quantitation of HERVK9 expression has the potential to provide prognostic prediction, which is crucial for determining the indications of upfront allo-HCT.

Publisher

Research Square Platform LLC

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