The long non-coding RNA overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics.

Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued. This latter phenomenon derived from RUNX1 transcriptional control, responsible for the stemness of hematopoietic precursors and for the block of differentiation in AML. By silencing AML mitochondrial mass decreased with augmented pharmacological sensitivity to mitochondria-targeting drugs the combination of tigecycline and cytarabine reduced leukemia progression in the AML-PDX model with high levels, supporting the concept of a mitochondrial vulnerability. Together, these findings uncover as crucial in myeloid differentiation and mitochondrial mass regulation.