PIWI 蛋白是干细胞相关的 RNA 结合蛋白，对生殖干细胞的存活至关重要。在癌症中，PIWI 蛋白过度表达。具体来说，PIWIL4 在多种癌症中高度表达，其中在急性髓系白血病 (AML) 中表达水平最高，这是一种由白血病干细胞 (LSC) 群体传播的侵袭性恶性肿瘤。巴梅扎伊等人。 (Blood Journal, Blood, 2023, 142, 90-105) 证明 PIWIL4 支持 AML 母细胞和 LSC，但对于健康的人类造血祖干细胞 (HSPC) 体内功能不是必需的。 PIWIL4 在 AML 中的作用是通过阻止 R 环在 LSC 持久性的关键基因中积累来发挥作用，这些基因涉及 DNA 损伤、复制应激和转录停滞。我们报道，暴露于分化剂的 THP-1 单核细胞中 PIWIL4 表达显着降低，表明 PIWIL4 在维持骨髓细胞未分化状态方面具有潜在作用。 PIWIL4 过度表达可能导致 LSC 的出现，从而推动白血病的增殖和维持。我们的研究结果与 Bamezai 等人报道的骨髓癌中 PIWIL4 的持续过度表达相关，并表明 PIWIL4 可能参与骨髓细胞分化。从这个角度来看，我们重点介绍 PIWI 通路在维持 AML 干性方面的影响的最新发现。此外，我们建议进一步研究 PIWI 通路在肿瘤发生和细胞分化中的作用，作为识别 AML 生物标志物和治疗靶点的策略。版权所有 © 2024 Garcia-Silva、Márquez 和 Pinello。

PIWI proteins are stem cell-associated RNA-binding proteins crucial for survival of germ stem cells. In cancer, PIWI proteins are overexpressed. Specifically, PIWIL4 is highly expressed in multiple cancers with the highest levels found in acute myeloid leukemia (AML), an aggressive malignancy propagated by a population of leukemia stem cells (LSCs). Bamezai et al. (Blood Journal, blood, 2023, 142, 90-105) demonstrated that PIWIL4 supports AML blasts and LSCs but is not necessary for healthy human hematopoietic progenitor stem cells (HSPCs) function in vivo. PIWIL4 in AML acts by preventing the accumulation of R-loops in key genes for LSCs persistence implicated in: DNA damage, replicative stress, and transcription arrest. We report that PIWIL4 expression significantly decreases in THP-1 monocytes exposed to a differentiating agent, suggesting a potential role for PIWIL4 in maintaining the undifferentiated state of myeloid cells. PIWIL4 overexpression could lead to the emergence of LSCs, driving leukemia propagation and maintenance. Our findings correlate with the persistent overexpression of PIWIL4 in myeloid cancers as reported by Bamezai et al., and suggest that PIWIL4 may be involved in myeloid cell differentiation. In this perspective, we highlight recent findings on the implication of PIWI pathway in maintaining AML stemness. Additionally, we propose further investigation on the role of PIWI pathway in oncogenesis and cellular differentiation as a strategy to identify biomarkers and therapeutic targets for AML.Copyright © 2024 Garcia-Silva, Márquez and Pinello.