Aberrant Expression of Non-Coding RNAs in Pediatric T Acute Lymphoblastic Leukemia and Their Potential Application as Biomarkers

Abstract

Less than 5% of the DNA sequence encodes for proteins, and the remainder encodes for non-coding RNAs (ncRNAs). Among the members of the ncRNA family, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play a pivotal role in the insurgence and progression of several cancers, including leukemia. Thought to have different molecular mechanisms, both miRNAs and lncRNAs act as epigenetic factors modulating gene expression and influencing hematopoietic differentiation, proliferation and immune system function. Here, we discuss the most recent findings on the main molecular mechanisms by which miRNAs and lncRNAs are involved in the pathogenesis and progression of pediatric T acute lymphoblastic leukemia (T-ALL), pointing out their potential utility as therapeutic targets and as biomarkers for early diagnosis, risk stratification and prognosis. miRNAs are involved in the pathogenesis of T-ALL, acting both as tumor suppressors and as oncomiRs. By contrast, to the best of our knowledge, the literature highlights lncRNAs as acting only as oncogenes in this type of cancer by inhibiting apoptosis and promoting cell cycle and drug resistance. Additionally, here, we discuss how these molecules could be detected in the plasma of T-ALL patients, highlighting that lncRNAs may represent a new class of promising accurate and sensitive biomarkers in these young patients. Thus, the unveiling of the aberrant signature of circulating and intracellular levels of lncRNAs could have great clinical utility for obtaining a more accurate definition of prognosis and uncovering novel therapeutic strategies against T-ALL in children. However, further investigations are needed to better define the standard methodological procedure for their quantification and to obtain their specific targeting in T-ALL pediatric patients.

Keywords: biomarkers; lncRNA; miRNA; pediatric T-ALL; therapeutic targets.

Figure 1

NGS workflow and ncRNA study. The NGS workflow for ncRNA study involves immunophenotyping cell sorting, RNA extraction and sequencing, differential expression analysis and experimental validation. This figure was created with BioRender (https://www.biorender.com, accessed on 15 March 2025).

Figure 2

ncRNAs in pediatric T-ALL. In the specific sections: (I) Description of the gold standard for classification, diagnosis and prognosis of pediatric T-ALL through cytology and genetic tests; (II) Deregulation of ncRNA (as miRNAs and lncRNAs) involved in neoplastic progression; (III) ncRNAs may be useful for stratifying patients and promoting personalized medicine. This figure was created with BioRender https://www.biorender.com, “accessed on 15 March 2025”.