Related Experiment Video
Updated: Jun 7, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations
Daniel T Starczynowski1, Ryan Morin, Andrew McPherson
1British Columbia Cancer Agency Research Centre, Vancouver, BC, Canada.
Abstract:
Cytogenetic alterations, such as amplifications, deletions, or translocations, contribute to myeloid malignancies. MicroRNAs (miRNAs) have emerged as critical regulators of hematopoiesis, and their aberrant expression has been associated with leukemia. Genomic regions containing sequence alterations and fragile sites in cancers are enriched with miRNAs; however, the relevant miRNAs within these regions have not been evaluated on a global basis. Here, we investigated miRNAs relevant to acute myeloid leukemia (AML) by (1) mapping miRNAs within leukemia-associated genomic alterations in human AML cell lines by high-resolution genome arrays and (2) evaluating absolute expression of these miRNAs by massively parallel small RNA sequencing. Seventy-seven percent (542 of 706) of miRNAs mapped to leukemia-associated copy-number alterations in the cell lines; however, only 18% (99 of 542) of these miRNAs are expressed above background levels. As evidence that this subset of miRNAs is relevant to leukemia, we show that loss of 2 miRNAs identified in our analysis, miR-145 and miR-146a, results in leukemia in a mouse model. Small RNA sequencing identified 28 putative novel miRNAs, 18 of which map to leukemia-associated copy-number alterations. This detailed genomic and small RNA analysis points to a subset of miRNAs that may play a role in myeloid malignancies.
Insights
Researchers identified microRNAs (miRNAs) linked to acute myeloid leukemia (AML) genomic alterations. Some miRNAs, like miR-145 and miR-146a, are crucial, as their loss caused leukemia in mice.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- Cytogenetic alterations are key drivers of myeloid malignancies.
- MicroRNAs (miRNAs) regulate hematopoiesis and are implicated in leukemia development.
- Genomic regions with alterations in cancer are often miRNA-rich, but their specific roles are underexplored.
Purpose of the Study:
- To globally map and evaluate miRNAs within leukemia-associated genomic alterations in acute myeloid leukemia (AML).
- To identify specific miRNAs that may play a role in the pathogenesis of myeloid malignancies.
Main Methods:
- High-resolution genome arrays were used to map miRNAs within leukemia-associated copy-number alterations in human AML cell lines.
- Massively parallel small RNA sequencing was employed to assess the absolute expression levels of these miRNAs.
- A mouse model was utilized to validate the relevance of identified miRNAs in leukemia development.
Main Results:
- 542 out of 706 (77%) miRNAs mapped to leukemia-associated copy-number alterations.
- Only 18% (99 of 542) of these mapped miRNAs showed expression above background levels.
- Loss of miR-145 and miR-146a in a mouse model resulted in leukemia, confirming their relevance.
- 28 putative novel miRNAs were identified, with 18 mapping to leukemia-associated copy-number alterations.
Conclusions:
- A subset of miRNAs located within leukemia-associated genomic alterations are expressed and potentially play a role in myeloid malignancies.
- miR-145 and miR-146a are critically involved in the development of leukemia.
- This study provides a comprehensive genomic and expression analysis of miRNAs in AML, highlighting potential therapeutic targets.
