Wnt/β‑catenin inhibition reverses multidrug resistance in pediatric acute lymphoblastic leukemia.

Although ~80% of newly diagnosed pediatric patients with acute lymphoblastic leukemia (ALL) become disease‑free following appropriate treatment, relapses frequently occur, with dismal prognosis. Therefore, it is urgent to develop novel therapeutic modalities. Resistance to chemotherapy is a major obstacle for the treatment of relapsed ALL. It has been indicated that Wnt pathway is potentially associated with leukemia recurrence. In the current study, a vincristine (VCR)‑resistant variant of the human ALL cell line BALL‑1 (BALL‑1/VCR) that also had relatively specific resistance to both doxorubicin and etoposide was generated. Over‑activation of the Wnt/β‑catenin signaling pathway was observed in BALL‑1/VCR cells, whereas Dickkopf‑related protein 1 selectively suppressed the Wnt signaling pathway and sensitized the response of BALL‑1/VCR to anticancer agents. In addition, prednisolone exposure in combination with Wnt inhibition restored chemo‑sensitivity in relapsed ALL blasts. Since the resistance of BALL‑1/VCR cells is potentially attributed to the overexpression of MDR‑associated protein 1 (MRP1), the development of drug resistance in relapsed ALL may associated with the overexpression of MRP1 and P‑glycoprotein. The results of this study demonstrated that, as a potential candidate to mimic relapsed ALL, BALL‑1/VCR could be used in further research, while Wnt‑inhibition may become a promising therapeutic approach for treating ALL.