Heidelberg,
23
November
2022
|
11:10
Europe/Amsterdam

How blood cancer cells renew themselves

Zusammenfassung

Scientists at Heidelberg University Hospital, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and HI-STEM gGmbH* have discovered a new mechanism for the self-renewal of leukemia stem cells / Study results help to better understand the aggressive course of acute myeloid leukemia / Publication in the journal Cancer Discovery / Joint press release by UKHD and DKFZ

Almost all tissues in our body contain a small number of stem cells that can divide indefinitely and are also capable of forming a large number of different mature cell types. Some cancer cells also acquire this ability and are then called cancer- or leukemia stem cells (LSCs) in case of some blood cancers. The presence and frequency of LSCs make blood cancers particularly aggressive and resistant to therapies. A team of researchers from Heidelberg University Hospital (UKHD), the German Cancer Research Center (DKFZ) and the Stem Cell Institute HI-STEM is investigating the molecular mechanisms that make up these leukemic stem cells in acute myeloid leukemia (AML). AML is a particularly aggressive cancer of the hematopoietic system. About 50 percent of patients suffer from a relapse after therapy, which is very hard to control and caused by surviving leukemia stem cells.
In the scientific journal "Cancer Discovery", the scientists describe a completely new molecular mechanism that turns normal leukemia cells into the particularly dangerous leukemia stem cells.

RNA methylation controls self-renewal mechanism and makes leukemic cells aggressive

The Heidelberg team focused its work on the group of molecules known as ribosomal ribonucleic acids (rRNA). Together with other components, rRNA forms the "protein factories" of cells, the ribosomes. Here, all proteins required for cell function are assembled from their components. Earlier research in Professor Dr. Müller-Tidow's team had suggested that certain chemical modifications (methylations) to rRNA may influence cancer development.

In their current study, the researchers first showed that AML stem cells carry highly specific and dynamically regulated methylation patterns on their rRNA molecules. They then transplanted human AML cells, which have been engineered to produce a key protein controlling this methylation process, into mice. This allowed them to functionally study the consequence of differential rRNA methylation in human leukemic cells in an in vivo setting. The data revealed that these methyl marks influence the type of proteins produced by the leukemia stem cells. Moreover, the ability to self-renew - the most important functional feature of aggressive leukemic stem cells - was also stimulated via this mechanism.

"Our work provides completely new insights into the molecular mechanisms that make leukemia stem cells so dangerous and that have been poorly understood since their discovery more than 20 years ago" explains Professor Dr. Andreas Trumpp, Head of the Division "Stem Cells and Cancer" at DKFZ and Director of HI-STEM. Professor Dr. Carsten Müller-Tidow, Medical Director of the Department of Hematology, Oncology and Rheumatology at the UKHD, reports: "We have known for a long time that methylation of the genetic material is an important control mechanism that regulates the aggressiveness of tumor cells. We have now been able to show for the first time that the methylation of rRNA molecules of cancer cells also has a significant influence on the course of the disease. We hope that, based on our results, we will be able to develop new therapeutic approaches in the future that will also destroy generally highly resistant leukemia stem cells and thus finally defeat leukemia."

* The Heidelberg Institute for Stem Cell Research and Experimental Medicine (HI-STEM) gGmbH was founded in 2008 as a public-private partnership by the DKFZ and Dietmar Hopp Foundation.

Literature

Zhou F, Aroua N, Rohde C, et al. A dynamic rRNA ribomethylome drives stemness in acute myeloid leukemia. Cancer Discov 2022; https://pubmed.ncbi.nlm.nih.gov/36259929/

Contact

Prof. Dr. Carsten Müller-Tidow
Medical Director of the Department of Hematology, Oncology, Rheumatology 
Heidelberg University Hospital
Im Neuenheimer Feld 410
69120 Heidelberg
Germany
Carsten.Mueller-Tidow@med.uni-heidelberg.de

Prof.  Dr. Andreas Trumpp
Head of Division Stem Cells and Cancer at the German Cancer Research Center (DKFZ) and Managing Director HI-STEM gGmbH
Im Neuenheimer Feld 280
69120 Heidelberg
Germany
a.trumpp@dkfz.de

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