Together, these results suggest that inhibiting any component in the β-catenin-SPI1-HAVCR2 regulatory circuit will inhibit LSC ‘stemness’ maintenance and lead to the effective elimination of HAVCR2-positive T-ALL cells in the presence of an effective debulking agent targeting the PI3K pathway, such as rapamycin or BAY1082439. The gene discussed is HAVCR2; the disease is acute lymphoblastic leukemia.