LncRNA AC021683.2 promotes chemotherapy resistance in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive clonal malignancy of hematopoietic progenitors with poor clinical outcomes. Though many patients respond well to induction chemotherapy, relapse occurs. The mechanisms underlying AML chemoresistance remain unclear. In our study, we performed whole transcriptome sequencing (WTS) on diagnosed AML samples sensitive or resistant to IA (idarubicin and cytarabine) induction treatment. We observed that lncRNA <i>AC021683.2</i> is upregulated in IA-resistant patients and associated with poor prognosis. <i>AC021683.2</i> depletion increased the chemosensitivity of AML cells to Ara-C both <i>in vitro</i> and <i>in vivo</i> by accelerating BCLAF1 ubiquitination and degradation, and <i>AC021683.2</i> depletion enhanced sensitivity partially by depending on BCLAF1. Both <i>AC021683.2</i> and BCLAF1 positively correlated with RAD50, which mediated their roles in Ara-C-resistant AML cells. These findings demonstrated that the lncRNA <i>AC021683.2</i> enhances the resistance of AML/Ara-C-resistant cells to Ara-C <i>in vitro</i> and <i>in vivo</i>, offering a potential target for treating Ara-C-resistant AML.