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Elucidating the role of long-non coding RNA in acute myeloid leukemia stem cells

Research Scholar

Marius Bill, physician, Department of Hematology and Oncology, University of Leipzig (Germany).
Clara D. Bloomfield, Faculty Mentor

Background

  • Hometown: Germany
  • Degrees received: Medical Degree, University of Leipzig, Germany; PhD in organic and medicinal chemistry, University of Leipzig, Germany.

What is the issue or problem addresses in your research?

In adult acute myeloid leukemia (AML) up to 60% of younger (<60 years) and 85% of older patients fail to attain long-term survival, despite intensive treatment. AML is a malignant disease that is characterized by the uncontrolled proliferation of immature myeloid cells, which have lost the ability to mature. Previously, it was believed AML consisted of only one type of cell, the leukemic blast. However, we now know that AML consists of multiple leukemic clones whose biology can vary drastically. One important AML cell subpopulation is the rare leukemic stem cell (LSC) population. These cells initiate disease, cause relapse, and are more resistant to standard leukemia treatments. Thus, understanding the biology of LSCs is crucial to improve patient outcome.

Long non-coding RNAs (lncRNAs) are longer than 200 nucleotides and regulate important cellular functions, such as imprinting, cell cycle, and differentiation. Our group previously showed that AML patients had different expression profiles of lncRNAs and that these profiles significantly associate with outcome. While this study indicates that lncRNAs are prognostic in AML, the expression and function of lncRNAs in LSCs are currently unknown. Our research focuses on identifying and validating lncRNAs involved in LSC biology that could be targeted therapeutically.

What methodology did you use in your research?

We analyzed 377 AML patients for LSC gene expression and correlated these data with lncRNA profiles and identified deregulated lncRNAs in LSCs. The biological role of one lncRNA, named DANCR, was further analyzed. We knocked-down DANCR using a transferrin/antibody labeled nanoparticle in vitro and in vivo.

What are the purpose/rationale and implications of your research?

A better understanding of LSCs is important to improve AML patient outcome. We identified for the first time a lncRNA expression signature that is associated with LSCs. We show that the lncRNA DANCR is overexpressed in LSCs, has a biological role and is targetable using a transferrin/antibody labeled nanoparticle.