An innovative cellular molecule may help transform the treatment and monitoring of pediatric acute lymphoblastic leukemia (pALL), one of the most common childhood cancers. Researchers have identified circulating long non-coding RNA HOTAIR as both a diagnostic and prognostic biomarker for pALL, paving the way for non-invasive monitoring of treatment efficacy and overcoming challenges associated with this aggressive disease.
Pediatric acute lymphoblastic leukemia, which is characterized by abnormal proliferation and differentiation of immature lymphoid cells, affects approximately 80% of childhood leukemia cases. Despite advancements, hurdles such as drug resistance complicate treatment outcomes significantly. To address the need for more effective monitoring strategies, researchers focused on long non-coding RNas due to their stability and resistance to degradation, making them attractive potential biomarkers for blood cancers.
The study, conducted at Omid Hospital (Isfahan, Iran), spanned from 2020 to 2023, with 50 pALL patient samples and 20 healthy controls analyzed using RT-qPCR. Notably, HOTAIR levels were found to be significantly elevated among pALL patients compared to controls. Establishing itself as more than just another RNA, HOTAIR exhibited over 95% specificity for cancer detection.
Notably, within the cohort of pALL patients, the expression of circulating HOTAIR dramatically decreased during chemotherapy treatment, particularly at the eight and twenty-month marks. This finding indicated treatment sensitivity and provided promising insights for its effectiveness as both a diagnostic and prognostic marker. The results indicate strong potential for HOTAIR levels to not only help diagnose pALL but also serve as measurable indicators of treatment success.
A key element of this research lies within the interactions between HOTAIR and miR-326, recognized as a tumor suppressor molecule. The current study posits HOTAIR acts as a sponge for miR-326, potentially sequestering it and impacting its functionality within cancerous cells. Enhanced HOTAIR levels at 24 and 48 hours post-transfection coincided with significant reductions of miR-326, thereby illustrating HOTAIR's ability to modulate the cancer suppressive effects of miR-326.
Researchers also observed HOTAIR's regulatory activity involved the GTPase RAB35, known to play pivotal roles in cell signaling and the secretion of exosomes—critical elements in intercellular communication. This implicates HOTAIR not only as a biomarker but also as part of the complex molecular network influencing pALL development and persistence.
These important findings reveal HOTAIR’s dual capacity to act as both a malignancy marker and facilitate the exosomal egress of miR-326, which may alter patient therapeutic responses. It is the first research to centralize HOTAIR’s potential role as both diagnostic and prognostic biomarker for pALL. The insights gleaned from this study highlight HOTAIR's practical application and future investigations could help refine diagnosis, predict treatment efficacy, and improve outcome for young patients battling this aggressive disease.
With the non-invasive nature of assessing circulating RNAB HOTAIR through blood samples, the research promises to alleviate the stress associated with traditional methods requiring more invasive sampling like bone marrow biopsies. Considering childhood acute lymphoblastic leukemia remains one of the challenging conditions, developing biomarkers like HOTAIR, which can advance the state of treatment monitoring, is imperative. Moving forward, future studies should assess larger patient populations to validate HOTAIR's diagnostic and prognostic capabilities comprehensively, potentially reforming standards for patient assessments and care.