function and expression alteration of lncRNAs in ALL

Acute lymphoblastic leukemia (ALL) is a malignancy characterized by a differentiation block at the B/T-precursor stage of lymphoid progenitors, leading to their invasion of bone marrow, peripheral blood, and extramedullary sites. These leukemic cells acquire resistance to apoptosis and differentiation, displaying hallmark cancer phenotypes such as continuous self-renewal, abnormal proliferation, and metastasis. The complexity of molecular and cytogenetic hallmarks in ALL results in significant heterogeneity, reflected in the different responses to therapeutic regimens. Relapse remains a leading cause of childhood cancer-related death, necessitating a comprehensive understanding of ALL’s etiology and progression. An increasing amount of data points to the important roles that regulatory non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), play in the genomic changes linked to ALL. LncRNAs are RNA molecules longer than ۲۰۰ nucleotides essential for controlling gene expression but do not encode proteins. Because of their altered expression, lncRNAs have a profound impact on the pathophysiology and development of ALL. Through a variety of processes, including epigenetic changes, transcriptional regulation, post-transcriptional regulation, and decreased interaction with microRNAs, upregulated long noncoding RNAs (lncRNAs) such as HOTAIR, MALAT۱, and TUG۱ promote leukemogenesis. On the other hand, epigenetic changes, genetic alterations, transcriptional regulation, and enhanced degradation can also be linked to the loss of tumor-suppressive effects in downregulated lncRNAs such as MEG۳, GAS۵, and LINC-PINT. LncRNAs also have a major impact on the prognosis, treatment response, and susceptibility of ALL. Certain single nucleotide polymorphisms (SNPs) in lncRNAs are linked to a higher risk of childhood ALL. High expression of the lncRNA BALR-۲ is associated with reduced mortality and poor response to therapy, while its reduction increases treatment sensitivity. Other lncRNAs, such as GAS۵ and RP۱۱-۱۳۷H۲.۴, are linked to treatment resistance. Additionally, lncRNAs serve as prognostic indicators; for instance, high levels of ZEB۱-AS۱ in B-ALL patients suggest a poor prognosis. In general, lncRNAs have a critical role in the pathophysiology, prognosis, and responsiveness to ALL therapy. Their genetic variants and altered expression offer important insights into disease causes and possible targets for treatment. In the long run, research on lncRNAs may be essential for ALL diagnosis, categorization, risk assessment, and therapy, leading to better patient outcomes and lower relapse rates. With a deeper understanding of lncRNAs in ALL, new therapeutic approaches may be developed, improving therapy precision and providing promise for more effective control of this aggressive malignancy.

کلیدواژه ها:

Department of Cell and Molecular Biology and Microbiology ، Faculty of Biological Science and Technology ، University of Isfahan ، Isfahan ، Iran