Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy with complex heterogenous genetic and biological nature. Thus, prognostic prediction and targeted therapies might contribute to better chemotherapeutic response. However, the emergence of multidrug resistance (MDR) markedly impedes chemotherapeutic efficacy and dictates poor prognosis. Therefore, prior evaluation of chemoresistance is of great importance in therapeutic decision making and prognosis. In recent years, preclinical studies on chemoresistance have unveiled a compendium of underlying molecular basis, which facilitated the development of targetable small molecules. Furthermore, routing genomic sequencing has identified various genomic aberrations driving cellular response during the course of therapeutic treatment through adaptive mechanisms of drug resistance, some of which serve as prognostic biomarkers in risk stratification. However, the underlying mechanisms of MDR have challenged the certainty of the prognostic significance of some mutations.

This review aims to provide a comprehensive understanding of the role of MDR in therapeutic decision making and prognostic prediction in AML. We present an updated genetic landscape of the predominant mechanisms of drug resistance with novel targeted therapies and potential prognostic biomarkers from preclinical and clinical chemoresistance studies in AML. We particularly highlight the unfolded protein response (UPR) that has emerged as a critical regulatory pathway in chemoresistance of AML with promising therapeutic horizon. Futhermore, we outline the most prevalent mutations associated with mechanisms of chemoresistance and delineate the future directions to improve the current prognostic tools. The molecular analysis of chemoresistance integrated with genetic profiling will facilitate decision making towards personalized prognostic prediction and enhanced therapeutic efficacy.

急性髓细胞性白血病（AML）是具有高度复杂的遗传和生物学特性的高度恶性血液恶性肿瘤。因此，预后预测和靶向治疗可能有助于更好的化疗反应。但是，多药耐药性（MDR）的出现显着阻碍了化学疗法的疗效，并预示了不良的预后。因此，化学抗药性的预先评估在治疗决策和预后中非常重要。近年来，有关化学抗性的临床前研究揭示了潜在的分子基础概述，这促进了可靶向小分子的发展。此外，路由基因组测序已通过耐药性的适应性机制确定了在治疗过程中驱动细胞应答的各种基因组异常，其中一些可作为风险分层中的预后生物标志物。但是，MDR的潜在机制已经挑战了某些突变的预后意义。

这篇综述旨在全面了解MDR在AML的治疗决策和预后预测中的作用。我们提出了一种新的靶向疗法和来自AML的临床前和临床化学抗药性研究的潜在预后生物标记物的耐药性主要机制的最新遗传景观。我们特别强调未折叠的蛋白质反应（UPR），它已成为具有良好治疗前景的AML化学耐药性的关键调节途径。此外，我们概述了与化学抗药性机制相关的最普遍的突变，并概述了改善当前预后工具的未来方向。