Role of Non-Coding RNAs in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia

Abstract

In the past decade, novel targeted therapy approaches, such as BTK inhibitors and Bcl2 blockers, and innovative treatments that regulate the immune response against cancer cells, such as monoclonal antibodies, CAR-T cell therapy, and immunomodulatory molecules, have been established to provide support for the treatment of patients. However, drug resistance development and relapse are still major challenges in CLL treatment. Several studies revealed that non-coding RNAs have a main role in the development and progression of CLL. Specifically, microRNAs (miRs) and tRNA-derived small-RNAs (tsRNAs) were shown to be outstanding biomarkers that can be used to diagnose and monitor the disease and to possibly anticipate drug resistance and relapse, thus supporting physicians in the selection of treatment regimens tailored to the patient needs. In this review, we will summarize the most recent discoveries in the field of targeted therapy and immunotherapy for CLL and discuss the role of ncRNAs in the development of novel drugs and combination regimens for CLL patients.

Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia

“…MiR-34a, targeting ZAP70 mRNA expression, is associated with the chemotherapy-refractory disease [84]. The downregulation of miR-34a and miR-125a upregulation was found to be associated with RS [85]. MiR-155 was reported as the most prevalent oncomiR in B-cell malignancies and revealed as a poor predictor for CLL, as well as an indicator to predict the therapy response [84,86].…”

hsa-miR-20b-5p and hsa-miR-363-3p Affect Expression of PTEN and BIM Tumor Suppressor Genes and Modulate Survival of T-ALL Cells In Vitro

“…Finally, our results bring to mind the perspective of testing the hypothetical therapeutic potential of antagonists of tumorigenic miRNAs, which might potentially prove beneficial for T-ALL patients, when combined with standard therapy or other therapeutic options [57][58][59]. Naturally, the potential benefits of such therapeutics would be limited to a well-defined subgroup of patients (with overexpression of hsa-miR-20b-5p and hsa-miR-363-3p), which falls into the idea of theragnostics and personalized targeted therapy in cancer [60].…”

Exosome: From leukemia progression to a novel therapeutic approach in leukemia treatment

“…Also, miR-155 regulates BAFF signaling thus positively affects BCR signaling which increases cancer proliferation. 50,51 S100-A9 is also a member of intracellular calciumbinding protein family and is associated with tumor progression. 52 S100-A9 protein is only detected in exosomes derived from patients with progressive stage of disease and is specifically overexpressed at the progressive stages of leukemia.…”

“…High expression of ROR1 in CLL cell is correlated with poor prognosis. 51,98 Cancer metastasis prediction can be also reached by the help of integrins within specific TDEs. 99 The important effect of myeloid-derived suppressor cells (MDSCs) on T cells leads us to discover their role in metastasis.…”

“…In this regard, the overexpression of miR‐155 in CLL patients has been associated with more aggressive and also poor chemotherapy responses. Also, miR‐155 regulates BAFF signaling thus positively affects BCR signaling which increases cancer proliferation 50,51 . S100‐A9 is also a member of intracellular calcium‐binding protein family and is associated with tumor progression 52 .…”