Aberrant expression of human endogenous retrovirus K9-derived elements is associated with better clinical outcome of acute myelocytic leukemia

TL;DR

Abnormal expression of a retrovirus-related element in leukemia patients is linked to better survival and immune response.

Contribution

This study identifies HERVK9-derived elements as a novel prognostic marker in AML, independent of existing risk factors.

Findings

HERVK9 expression is associated with improved event-free survival in AML patients.

Higher HERVK9 levels correlate with enhanced antigen presentation and immune response genes.

HERVK9 may serve as a prognostic indicator for allogeneic hematopoietic cell transplantation in AML.

Abstract

Acute myelocytic leukemia (AML) is a common hematological malignancy in adults. Although several risk stratifications based on cytogenetic and molecular abnormalities are available to guide the indications for allogeneic hematopoietic cell transplantation (allo-HCT), determining optimal treatment strategies for AML remains challenging. In this study, using transcriptome datasets, we investigated the association between event-free survival (EFS) in intensively treated AML patients and the aberrant expression of endogenous viral element (EVE)-derived open reading frames (ORFs), which have been reported to be associated with the pathophysiology of various malignancies and have the potential to serve as neoantigens in specific cancers.

The expression levels of human endogenous retrovirus family K9 (HERVK9) ORFs were associated with EFS, independent of conventional risk stratification. Furthermore, AML cells with higher levels of HERVK9 expression exhibited enhanced antigen processing and presentation, along with increased expression of genes associated with adaptive immune responses and apoptosis, indicating that aberrant HERVK9 expression may initiate an anti-neoplastic immune response via increased antigen presentation.

HERVK9 expression may have serve as a crucial prognostic indicator that could aid in determining the indications for upfront allo-HCT in AML patients.

The online version contains supplementary material available at 10.1186/s12977-025-00661-6.

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