RGS1 is an effective T-cell marker of acute myeloid leukemia remission after hematopoietic stem cell transplantation

Abstract

Disease relapse is a major cause of death in acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The characterization of novel functional T-cell subtypes is critical for predicting clinical responses as well as developing strategies for immunotherapy in leukemia. We used single-cell RNA-sequencing to resolve the T cells' profiles of AML patients who had a relapse (RL) or reached complete remission (CR) after HSCT and addressed the characteristics of T cells at molecular level under HSCT scenario. Ten T-cell subtypes were identified in these RL and CR patient groups, of which mature T cells subtypes, such as CD8+ T effector memory (TEM), CD8+ T effector (TEFF), CD4+ TEM, and CD4+ TEFF cells, tended to be more abundant in the CR group, while naïve CD8, naïve CD4, and exhausted CD8+ T cells occupied larger proportions in the RL group. Of note, we identified that RGS1 (regulator of G-protein signaling 1) highly expressing CD8+ TEFFs tended to enrich in the CR group. Higher levels of RGS1 in CD8+ TEFF, CD8+ T, and CD3+ T cells were significantly associated with remission after HSCT in AML patients, which could also predict clinical outcomes after allo-HSCT. And the elevation of RGS1 levels in CD8+ T cells increased cytotoxic factor production, possibly by activating the NF-κB signaling pathway. These findings provide valuable insights into T-cell characteristics under allo-HSCT and identify RGS1 as a new marker potentially predicting clinical responses for AML after allo-HSCT.

Keywords: RGS1; T cells; allo-HSCT for AML; single-cell RNA sequencing.