NRAS and KRAS activating point mutations are present in 10–30% of myeloid malignancies and are often associated with a proliferative phenotype. RAS mutations harbor allele-specific structural and biochemical properties depending on the hotspot mutation, contributing to variable biological consequences. Given their subclonal nature in most myeloid malignancies, their clonal architecture, and patterns of cooperativity with other driver genetic alterations may potentially have a direct, causal influence on the prognosis and treatment of myeloid malignancies. RAS mutations overall tend to be associated with poor clinical outcome in both chronic and acute myeloid malignancies. Several recent prognostic scoring systems have incorporated RAS mutational status. While RAS mutations do not always act as independent prognostic factors, they significantly influence disease progression and survival. However, their clinical significance depends on the type of mutation, disease context, and treatment administered. Recent evidence also indicates that RAS mutations drive resistance to targeted therapies, particularly FLT3, IDH1/2, or JAK2 inhibitors, as well as the venetoclax-azacitidine combination. The investigation of novel therapeutic strategies and combinations that target multiple axes within the RAS pathway, encompassing both upstream and downstream components, is an active field of research. The success of direct RAS inhibitors in patients with solid tumors has brought renewed optimism that this progress will be translated to patients with hematologic malignancies. In this review, we highlight key insights on RAS mutations across myeloid malignancies from the past decade, including their prevalence and distribution, cooperative genetic events, clonal architecture and dynamics, prognostic implications, and therapeutic targeting.

NRAS和KRAS激活点突变存在于 10-30% 的骨髓恶性肿瘤中，并且通常与增殖表型相关。RAS突变具有等位基因特异性结构和生化特性，具体取决于热点突变，从而导致不同的生物学后果。鉴于它们在大多数骨髓恶性肿瘤中的亚克隆性质，它们的克隆结构以及与其他驱动基因改变的协同模式可能对骨髓恶性肿瘤的预后和治疗产生直接的因果影响。总体而言， RAS突变往往与慢性和急性髓系恶性肿瘤的不良临床结果相关。最近的几个预后评分系统已纳入RAS突变状态。虽然RAS突变并不总是作为独立的预后因素，但它们显着影响疾病进展和生存。然而，它们的临床意义取决于突变类型、疾病背景和治疗。最近的证据还表明，RAS突变会导致对靶向治疗的耐药性，特别是 FLT3、IDH1/2 或 JAK2 抑制剂以及维奈托克 - 阿扎胞苷组合。针对 RAS 通路内多个轴（涵盖上游和下游成分）的新型治疗策略和组合的研究是一个活跃的研究领域。直接 RAS 抑制剂在实体瘤患者中的成功让人们重新乐观起来，这一进展将转化为血液恶性肿瘤患者。在这篇综述中，我们重点介绍了过去十年间髓系恶性肿瘤中RAS突变的重要见解，包括其患病率和分布、协同遗传事件、克隆结构和动态、预后影响和治疗靶向。