DHX9 as a prognostic biomarker and its biological roles in acute myeloid leukemia

Background: Acute myeloid leukemia (AML) is a highly malignant hematopoietic disease, with low remission and high relapse rates, and there is currently no effective treatment except for acute promyelocytic leukemia. DExH-Box Helicase 9, a member of the DExD/H-box family of helicases, is highly expressed in some solid tumors and associated with poor prognosis. However, its role in AML has not been reported. This study aimed to investigate the clinical significance and biological roles of DHX9 in AML.

Methods: Specific gene primers and TaqMan probes were prepared to construct absolute quantitative methods for DHX9. Receiver operating characteristic curves were constructed to evaluate the diagnostic and prognostic value of DHX9. Series of shRNA-mediated DHX9 knockdown experiments to assess the functional roles of DHX9 such as proliferation, cell cycle, Apoptosis and differentiation ability. In addition, bioinformatic analysis was used to find out which potential pathways DHX9 participated in.

Results: A detection method for DHX9 was successfully established. DHX9 was highly expressed in the AML patients with aberrant myeloid blasts. Significant differences were found among patients with different risk levels, with high levels of DHX9 related to a poor prognosis. shRNA-mediated DHX9 knockdown significantly inhibited the proliferation and cell cycle, and induced Apoptosis and differentiation in THP-1 and MOLM-13 cells. Further bioinformatic analysis showed that DHX9 expression was significantly associated with metabolism pathways, suggesting that DHX9 may be involved in the metabolic reprogramming of AML blasts.

Conclusions: Our study discovers that DHX9 promotes AML development and may serve as a biomarker for AML, holding a better prospect for clinical application.

Acute myeloid leukemia; Apoptosis; Biomarker; DExH-Box helicase 9; Proliferation.