ORLANDO – Researchers at Hannover Medical School in Hannover, Germany, have established a core long non-coding RNA (lncRNA) stem cell signature in acute myeloid leukemia (AML), a study presented at the American Society of Hematology (ASH) 57th Annual Meeting & Exposition has shown.1
LncRNAs and microRNAs have been found to be critical regulators of gene expression, epigenetics, and cell fate decisions.
“Blood cells have a unique lncRNA expression pattern,” Adrian Schwarzer, MD, PhD, of the Institute of Experimental Hematology at Hannover Medical School in Hannover, Germany, said during his presentation. “Lineage-specific lncRNAs regular human hematopoiesis.”
Therefore, researchers sought to conduct an integrate and functional analysis of the microRNA-, lncRNA, and mRNA-transcriptome of purified human hematopoietic stem cells and correlate them with non-coding RNA (ncRNA) expression profile of 46 pediatric AML samples.
Results of the analysis showed a strong and highly coordinated upregulation of microRNAs, small nucleolar RNAS, and lncRNAs within the DLK1-DIO3 locus on chromosome 14, particularly in megakaryoctyes. Researchers found that short hairpin RNA-mediated knock-down of the lncRNA MEG3 decreased erythroid colony formation and megakaryocytic cell proliferation, demonstrating the functional significance of this non-coding RNA locus on chromosome 14. Two lnRNAs (LINC00173 and DY635655) also reduced proliferation of myeloid NB4 cells.
“LINC00173 is important for growth and maturation during granulopoiesis,” Dr Schwarzer said.
Researchers also identified a stem-cell associated with lncRNA signature that was not present in healthy differentiated blood cells, but was upregulated in the pediatric AML samples. AML samples that did not have upregulation of these lncRNAs had suppressed upregulation of differentiation-associated lncRNAs, thereby retaining the global identify of myeloid progenitor cells.
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“Leukemias can be clustered according to their lncRNA expression profile,” Dr Schwarzer concluded. “Our dataset can be used to identify potential noncoding disease drivers in acute leukemia.”
- Schwarzer A, Emmrich S, Schmidt F, et al. Integrated analysis of the human hematopoietic non-coding RNA landscape reveals lnc-RNA stem cell signature in AML. Oral presentation at:the American Society of Hematology (ASH) 57th Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.