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Non-Coding RNAs Are Implicit in Chronic Myeloid Leukemia Therapy Resistance
Alexander Rudich1, Ramiro Garzon1, Adrienne Dorrance1
1Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Abstract:
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm initiated by the presence of the fusion gene BCR::ABL1. The development of tyrosine kinase inhibitors (TKIs) highly specific to p210-, the constitutively active tyrosine kinase encoded by BCR::ABL1, has greatly improved the prognosis for CML patients. Now, the survival rate of CML nearly parallels that of age matched controls. However, therapy resistance remains a persistent problem in the pursuit of a cure. TKI resistance can be attributed to both BCR::ABL1 dependent and independent mechanisms. Recently, the role of non-coding RNAs (ncRNAs) has been increasingly explored due to their frequent dysregulation in a variety of malignancies. Specifically, microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs) have been shown to contribute to the development and progression of therapy resistance in CML. Since each ncRNA exhibits multiple functions and is capable of controlling gene expression, they exert their effect on CML resistance through a diverse set of mechanisms and pathways. In most cases ncRNAs with tumor suppressing functions are silenced in CML, while those with oncogenic properties are overexpressed. Here, we discuss the relevance of many aberrantly expressed ncRNAs and their effect on therapy resistance in CML.
Insights
Non-coding RNAs (ncRNAs) like miRNAs, circRNAs, and lncRNAs are key drivers of therapy resistance in chronic myeloid leukemia (CML). Understanding their dysregulation is crucial for overcoming treatment challenges and finding a cure for CML.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR-ABL1 fusion gene.
- Tyrosine kinase inhibitors (TKIs) have significantly improved CML patient outcomes, but therapy resistance remains a challenge.
- Non-coding RNAs (ncRNAs) are increasingly recognized for their role in cancer development and treatment resistance.
Purpose of the Study:
- To explore the role of aberrantly expressed ncRNAs in CML therapy resistance.
- To discuss the mechanisms by which ncRNAs influence TKI resistance in CML.
- To highlight the potential of targeting ncRNAs for novel CML therapies.
Main Methods:
- Review of current literature on ncRNAs in CML.
- Analysis of dysregulation patterns of microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs) in CML.
- Discussion of ncRNA-mediated mechanisms of TKI resistance.
Main Results:
- ncRNAs, including miRNAs, circRNAs, and lncRNAs, are frequently dysregulated in CML.
- Aberrantly expressed ncRNAs contribute to both BCR-ABL1 dependent and independent TKI resistance.
- Tumor-suppressing ncRNAs are often silenced, while oncogenic ncRNAs are overexpressed in CML.
Conclusions:
- ncRNAs play a significant role in the development and progression of TKI resistance in CML.
- Targeting specific ncRNAs may offer a promising strategy to overcome CML therapy resistance.
- Further research into ncRNA function and regulation is essential for advancing CML treatment.
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