The oxysterol-binding protein-related proteins (ORPs) have emerged as orchestrators of phosphatidylinositol-4,5-bisphosphate (PIP₂) and cholesterol trafficking to the plasma membrane (PM). In this scenario, recent studies raised the prospect of ORPs cooperative behavior in sustaining leukemia stem cells (LSCs) survival by remotely enhancing ER-mitochondria Ca²⁺ communication. At the apex of the signaling cascade, the aberrantly upregulated LSC-ORP4L fosters PM-PIP₂ extraction & cleavage, endoplasmic reticulum (ER)-Ca²⁺ release and mitochondrial energetics. The theoretical ember of draining fuel from the chemoresistant LSCs by restraining endoplasmic reticulum (ER)-mitochondria Ca²⁺ fluxes in a lipid-contingent fashion ensues. In light of relevant literature, this review briefly and critically discusses some key molecular ins & outs underlying such therapeutic opportunity in acute myeloid leukemia (AML).

氧固醇结合蛋白相关蛋白 (ORP) 已成为磷脂酰肌醇 4,5-二磷酸 (PIP ₂ ) 和胆固醇运输至质膜 (PM) 的协调者。在这种情况下，最近的研究提出了 ORP 合作行为通过远程增强 ER-线粒体 Ca ²⁺通讯来维持白血病干细胞 (LSC) 存活的前景。在信号级联的顶点，异常上调的 LSC-ORP4L 促进 PM-PIP ₂提取和切割、内质网 (ER)-Ca ²⁺释放和线粒体能量学。通过抑制内质网 (ER)-线粒体 Ca ²⁺从耐化学性 LSC 中排出燃料的理论余烬随之而来的是脂类偶然方式的通量。根据相关文献，本综述简要且批判性地讨论了在急性髓系白血病 (AML) 中这种治疗机会背后的一些关键分子来龙去脉。