MicroRNA Regulation in Chronic Myeloid Leukemia

Chronic myeloid leukaemia (CML) is driven by the BCR-ABL1 fusion oncoprotein which orchestrates dysregulated tyrosine kinase signalling and perturbs normal haematopoietic differentiation. MicroRNAs (miRNAs), a class of small non-coding RNAs that modulate gene expression post-transcriptionally, have emerged as key regulators of leukemogenesis, disease progression and response to therapy. Aberrant miRNA profiles influence crucial pathways such as those controlling cell cycle, apoptosis and signal transduction, contributing to drug resistance and persistence of leukemic stem cells. Advances in miRNA biology have highlighted both mechanistic links to MAPK and PI3K-Akt cascades and the potential of circulating miRNAs as minimally invasive biomarkers. Current efforts aim to harness this regulatory layer for refined risk stratification, to predict treatment response and to develop novel therapeutic strategies targeting miRNA networks, offering promise for improved patient outcomes worldwide.

Research from Nature Portfolio

Recent studies have demonstrated that baseline expression levels of miR-21 and miR-451 in blood samples can stratify patients according to their likelihood of achieving an optimal response to tyrosine kinase inhibitor therapy. Higher miR-451 levels at diagnosis correlated with superior molecular response at six and twelve months, while elevated miR-21 was associated with suboptimal outcomes. A combined miRNA signature was used to construct a predictive model, enhancing the precision of early treatment decision-making and offering a practical approach to personalise therapeutic regimens.

MicroRNA Regulation in Chronic Myeloid Leukemia publication trend

The graph below shows the total number of articles in microrna regulation in chronic myeloid leukemia across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): A short non-coding RNA molecule that regulates gene expression by targeting messenger RNAs for degradation or translational repression.

BCR-ABL1: A fusion protein with constitutive tyrosine kinase activity resulting from the t(9;22) translocation, which drives CML pathogenesis.

Tyrosine Kinase Inhibitor (TKI): A class of targeted therapy that blocks the aberrant kinase activity of BCR-ABL1 to control disease progression.

Leukemic Stem Cell (LSC): A rare subpopulation of CML cells with self-renewal capacity that can persist despite therapy and contribute to disease relapse.

Biomarker: A measurable indicator of a biological condition, used for diagnosis, prognosis or monitoring of disease.

MAPK Pathway: A signalling cascade involving mitogen-activated protein kinases that regulates cell proliferation, differentiation and survival, often dysregulated in CML.

References

1. The Screening of microRNAs in Chronic Myeloid Leukemia: A Clinical Evaluation. International Journal of Molecular Sciences (2024).
2. MicroRNAs mediated regulation of MAPK signaling pathways in chronic myeloid leukemia. Oncotarget (2016).
3. Deregulated expression of miR-29a-3p, miR-494-3p and miR-660-5p affects sensitivity to tyrosine kinase inhibitors in CML leukemic stem cells. Oncotarget (2017).
4. Expression differences of miR-142-5p between treatment-naïve chronic myeloid leukemia patients responding and non-responding to imatinib therapy suggest a link to oncogenic ABL2, SRI, cKIT and MCL1 signaling pathways critical for development of therapy resistance. Experimental Hematology & Oncology (2020).
5. MicroRNA signature refine response prediction in CML. Scientific Reports (2019).