lncDDR suppresses drug resistance by regulating DNA damage repair through ILF2-YB1 in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a prevalent hematologic malignancy in pediatric and adolescent populations, characterized by uncontrolled proliferation of immature T lymphocytes. The development of chemoresistance represents a major clinical challenge in T-ALL treatment and alteration in DNA damage response (DDR) pathways was recognized as important mechanism underlying drug resistance. Long non-coding RNAs (lncRNAs), defined as transcripts exceeding 200 nucleotides in length, have emerged as critical regulators in various pathological processes, including oncogenesis. However, their specific roles in DDR regulation within T-ALL remain largely unexplored. In this study, through comprehensive sequencing analysis of clinical specimens, we identified that lncDDR was significantly upregulated in T-ALL patients. Functional characterization revealed that lncDDR promotes leukemogenesis by enhancing tumor cell proliferation both in vitro and in vivo. Utilizing RNA pull-down assays coupled with mass spectrometric analysis, we identified ILF2 (interleukin enhancer-binding factor 2) as a direct interacting partner of lncDDR. Given the established involvement of ILF2 in DDR processes, we subsequently investigated the functional role of lncDDR in modulating DDR pathways in T-ALL. Additionally, we systematically evaluated the impact of lncDDR on chemosensitivity in T-ALL treatment.