LncRNA AC021683.2 promotes chemotherapy resistance in acute myeloid Leukemia

Abstract

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 AC021683.2 is upregulated in IA-resistant patients and associated with poor prognosis. AC021683.2 depletion increased the chemosensitivity of AML cells to Ara-C both in vitro and in vivo by accelerating BCLAF1 ubiquitination and degradation, and AC021683.2 depletion enhanced sensitivity partially by depending on BCLAF1. Both AC021683.2 and BCLAF1 positively correlated with RAD50, which mediated their roles in Ara-C-resistant AML cells. These findings demonstrated that the lncRNA AC021683.2 enhances the resistance of AML/Ara-C-resistant cells to Ara-C in vitro and in vivo, offering a potential target for treating Ara-C-resistant AML.