RMRP-Induced Chemo-Resistance in Relapsed and Refractory Acute Myeloid Leukemia via Mitochondrial Dysfunction

Relapsed and refractory acute myeloid leukemia (R/R AML) has a poor prognosis due to chemotherapy resistance. Mitochondrial dysfunction contributes to this resistance, but the role of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in R/R AML remains unclear. Mass spectrometry identified molecules linked to chemoresistance in AML. The role of RMRP was examined by assessing its impact on mitochondrial transfer in the AML bone marrow microenvironment. Transmission electron microscopy and western blotting were used to study mitochondrial function and autophagy in RMRP-knockdown AML cells. RMRP was overexpressed in R/R AML, and its silencing sensitized AML cells to chemotherapy drugs. RMRP knockdown reduced mitochondrial respiratory capacity, mtDNA copy numbers, and mitochondrial gene transcription. It also led to altered mitophagy markers and decreased mitochondrial methylation. Immunoprecipitation revealed RMRP-TERT complex formation, suggesting a role in post-transcriptional regulation of mitochondrial function and ROS production. High RMRP expression in R/R AML is linked to mitochondrial dysfunction and chemotherapy resistance, providing new insights into potential therapeutic strategies to overcome drug resistance in this disease.