Long Non-Coding RNAs in Leukemia: A Novel Frontier for Diagnostic Biomarkers

Long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNA molecules that have gained attention for their roles in gene regulation and disease progression, including hematological malignancies like leukemia. Leukemia is a group of heterogeneous cancers that affect the blood and bone marrow, including subtypes such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Recent studies suggest that lncRNAs can serve as novel diagnostic biomarkers due to their distinct expression profiles in different leukemia subtypes, offering non-invasive, precise tools for early diagnosis and disease monitoring. Objective: To summarize the diagnostic and prognostic applications of lncRNAs in leukemia, highlighting key lncRNAs associated with various subtypes and their potential to improve diagnostic accuracy and patient risk stratification. Methods: A literature review was conducted on studies exploring lncRNA expression and functional roles in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL), emphasizing those demonstrating diagnostic or prognostic utility. Key Findings: A range of lncRNAs show promising potential as biomarkers across all major leukemia types. In AML, downregulation of the tumor suppressor MEG۳ is associated with poor prognosis, with studies highlighting its role in modulation of p۵۳ signaling. MEG۳ hypermethylation occurs in approximately half of AML cases, suggesting utility for early diagnosis. RUNXOR is significantly upregulated in AML, acting by regulating RUNX۱ and contributing to leukemogenic chromosomal translocations. UCA۱ is expressed in CEBPA-mutated AML and promotes cell proliferation by inhibiting the tumor suppressor p۲۷. In ALL, ANRIL is over-expressed, particularly in Philadelphia chromosome-positive (Ph+) ALL, affecting cell cycle regulation via the INK۴/ARF locus. T-ALL-R-LncR۱ is highly expressed in T-cell ALL, inhibiting apoptosis and conferring treatment resistance, while LUNAR۱ induces IGF۱R expression and leukemic cell survival, rendering it a potential diagnostic and prognostic marker. In CML, H۱۹ is implicated in Bcr-Abl-mediated transformation and imatinib resistance. LncRNA-BGL۳ acts as a competing endogenous RNA, up-regulating miR-۱۷ and miR-۹۳ to regulate PTEN, promoting apoptosis and serving as a marker for therapeutic response. In CLL, lincRNA-p۲۱ is down-regulated, particularly in cases with ۱۷p۱۳ deletion harboring TP۵۳, associated with aggressive disease. DLEU۱ and DLEU۲, located in the frequently deleted ۱۳q۱۴ region, are associated with disease severity and prognosis, making them promising diagnostic candidates. Conclusion: LncRNAs represent a novel class of diagnostic biomarkers for leukemia, providing molecular signatures with potential for early detection, subtype classification, and treatment monitoring. Their differential expression across subtypes underscores their value as non-invasive biomarkers complementing existing diagnostics. However, further research and clinical validation are necessary for routine integration into leukemia diagnostics.

کلیدواژه ها:

Long non-coding RNAs(lncRNAs) ، Leukemia diagnosis ، Leukemia Biomarkers ، Molecular diagnosis