H12O-CNIO Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, Spain.
Department of Hematology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain.
Int J Mol Sci. 2022 Aug 23;23(17):9552. doi: 10.3390/ijms23179552.
Hematological malignancies comprise a plethora of different neoplasms, such as leukemia, lymphoma, and myeloma, plus a myriad of dysplasia, such as myelodysplastic syndromes or anemias. Despite all the advances in patient care and the development of new therapies, some of these malignancies remain incurable, mainly due to resistance and refractoriness to treatment. Therefore, there is an unmet clinical need to identify new biomarkers and potential therapeutic targets that play a role in treatment resistance and contribute to the poor outcomes of these tumors. RNA-binding proteins (RBPs) are a diverse class of proteins that interact with transcripts and noncoding RNAs and are involved in every step of the post-transcriptional processing of transcripts. Dysregulation of RBPs has been associated with the development of hematological malignancies, making them potential valuable biomarkers and potential therapeutic targets. Although a number of dysregulated RBPs have been identified in hematological malignancies, there is a critical need to understand the biology underlying their contribution to pathology, such as the spatiotemporal context and molecular mechanisms involved. In this review, we emphasize the importance of deciphering the regulatory mechanisms of RBPs to pinpoint novel therapeutic targets that could drive or contribute to hematological malignancy biology.
血液系统恶性肿瘤包括多种不同的肿瘤，如白血病、淋巴瘤和骨髓瘤，以及多种发育异常，如骨髓增生异常综合征或贫血。尽管在患者护理方面取得了所有进展，并开发了新的治疗方法，但其中一些恶性肿瘤仍然无法治愈，主要是由于对治疗的耐药性和抵抗性。因此，临床上需要确定新的生物标志物和潜在的治疗靶点，这些生物标志物和潜在的治疗靶点在治疗耐药性中起作用，并导致这些肿瘤的预后不良。RNA 结合蛋白（RBPs）是一类具有多样性的蛋白质，它们与转录本和非编码 RNA 相互作用，并参与转录本的转录后加工的每一个步骤。RBPs 的失调与血液系统恶性肿瘤的发生有关，使它们成为有潜在价值的生物标志物和潜在的治疗靶点。尽管已经在血液系统恶性肿瘤中鉴定出许多失调的 RBPs，但仍迫切需要了解它们对病理学的贡献的生物学基础，例如涉及的时空背景和分子机制。在这篇综述中，我们强调了解 RBP 调节机制的重要性，以确定可能驱动或有助于血液系统恶性生物学的新的治疗靶点。
