Kirtonia Anuradha, Ashrafizadeh Milad, Zarrabi Ali, Hushmandi Kiavash, Zabolian Amirhossein, Bejandi Atefe K, Rani Reshma, Pandey Amit K, Baligar Prakash, Kumar Vinit, Das Bhudev C, Garg Manoj
Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh, India.
Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Tuzla, Istanbul, Turkey.
J Cell Physiol. 2022 Jan;237(1):450-465. doi: 10.1002/jcp.30590. Epub 2021 Sep 27.
Acute myeloid leukemia (AML) is a common hematological disorder with heterogeneous nature that resulted from blocked myeloid differentiation and an enhanced number of immature myeloid progenitors. During several decades, different factors, including cytogenetic, genetic, and epigenetic have been reported to contribute to the pathogenesis of AML by inhibiting the differentiation and ensuring the proliferation of myeloid blast cells. Recently, long noncoding RNAs (lncRNAs) have been considered as potential diagnostic, therapeutic, and prognostic factors in different human malignancies including AML. Altered expression of lncRNAs is correlated with the transformation of hematopoietic stem and progenitor cells into leukemic blast cells because of their distinct role in the key cellular processes. We discuss the significant role of lncRNAs in the proliferation, survival, differentiation, leukemic stem cells in AML and their involvement in different molecular pathways (insulin-like growth factor type I receptor, FLT3, c-KIT, Wnt, phosphatidylinositol 3-kinase/protein kinase-B, microRNAs), and associated mechanisms such as autophagy, apoptosis, and glucose metabolism. In addition, we aim to highlight the role of lncRNAs as reliable biomarkers for diagnosis, prognosis, and drug resistance for precision medicine in AML.
急性髓系白血病(AML)是一种常见的血液系统疾病,具有异质性,由髓系分化受阻和未成熟髓系祖细胞数量增加所致。几十年来,据报道包括细胞遗传学、遗传学和表观遗传学在内的不同因素通过抑制分化和确保髓系原始细胞的增殖而导致AML的发病机制。最近,长链非编码RNA(lncRNAs)被认为是包括AML在内的不同人类恶性肿瘤中的潜在诊断、治疗和预后因素。lncRNAs表达的改变与造血干细胞和祖细胞向白血病原始细胞的转化相关,因为它们在关键细胞过程中具有独特作用。我们讨论lncRNAs在AML的增殖、存活、分化、白血病干细胞中的重要作用,以及它们参与的不同分子途径(胰岛素样生长因子I型受体、FLT3、c-KIT、Wnt、磷脂酰肌醇3激酶/蛋白激酶B、微小RNA),以及自噬、凋亡和葡萄糖代谢等相关机制。此外,我们旨在强调lncRNAs作为AML精准医学诊断、预后和耐药性可靠生物标志物的作用。