Nav: Home

Scientists discover how rogue communications between cells lead to leukemia

February 06, 2020

New research has deciphered how rogue communications in blood stem cells can cause Leukaemia.

The discovery could pave the way for new, targeted medical treatments that block this process.

Blood cancers like leukaemia occur when mutations in stem cells cause them to produce too many blood cells.

An international team of scientists, including researchers at the University of York, have discovered how these mutations allow cells to deviate from their normal method of communicating with each other, prompting the development of blood cells to spiral out of control.

The scientists used super-resolution fluorescent microscopy to study the way blood stem cells talk to each other in real time.

They observed how cells receive instructions from 'signalling proteins', which bind to a receptor on the surface of another cell before transmitting a signal telling the cell how to behave.

Blood stem cells communicate via cytokines, which are one of the largest and most diverse families of signalling proteins and are critical for the development of blood cells and the immune system.

Understanding this process led researchers to the discovery that mutations associated with certain types of blood cancers can cause blood stem cells to 'go rogue' and communicate without cytokines.

The stem cells begin to transmit uncontrolled signals causing the normal system of blood cell development to become overrun, producing an imbalance of healthy white and red blood cells and platelets.

Professor Ian Hitchcock from the York Biomedical Research Institute and the Department of Biology at the University of York, said: "Our bodies produce billions of blood cells every day via a process of cells signalling between each other. Cytokines act like a factory supervisor, tightly regulating this process and controlling the development and proliferation of the different blood cell types.

"Our observations led us to a previously unknown mechanism for how individual mutations trigger blood stem cells to start signalling independently of cytokines, causing the normal system to become out of control and leading to diseases like leukaemia.

"Understanding this mechanism may enable the identification of targets for the development of new drugs."

This research team used a combination of molecular modelling, structural biology, biophysics, super-resolution microscopy and cell biology to demonstrate for the first time that these specific receptors on the surface of blood stem cells are linked by cytokines to form pairs.

Co-author of the study, Professor Jacob Piehler from Osnabrück University, said: "By directly visualising individual receptors at physiological conditions under the microscope, we were able to resolve a controversy that has preoccupied the field for more than 20 years."

Professor Ilpo Vattulainen from the University of Helsinki, added: "Our biomolecular simulations unveiled surprising features concerning the orientation of active receptor pairs at the plasma membrane, explaining how mutations render activation possible without a ligand (such as a cytokine). These predictions were subsequently confirmed experimentally"

First author Dr. Stephan Wilmes, who started the project as a Postdoc at Osnabrück University before moving to the University of Dundee: "It was truly inspiring to tackle this highly relevant biomedical question by applying cutting-edge biophysical techniques. Here in Dundee, I had the chance to perform complementary activity assays, which corroborated our mechanistic model."
-end-
The study is published in the journal Science and was carried out in collaboration between the universities of York, Dundee, Osnabruck (Germany), Helsinski (Finland), Stanford and New York (USA).

University of York

Related Stem Cells Articles:

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.
First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
TSRI researchers identify gene responsible for mesenchymal stem cells' stem-ness'
Researchers at The Scripps Research Institute recently published a study in the journal Cell Death and Differentiation identifying factors crucial to mesenchymal stem cell differentiation, providing insight into how these cells should be studied for clinical purposes.
More Stem Cells News and Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#555 Coronavirus
It's everywhere, and it felt disingenuous for us here at Science for the People to avoid it, so here is our episode on Coronavirus. It's ok to give this one a skip if this isn't what you want to listen to right now. Check out the links below for other great podcasts mentioned in the intro. Host Rachelle Saunders gets us up to date on what the Coronavirus is, how it spreads, and what we know and don't know with Dr Jason Kindrachuk, Assistant Professor in the Department of Medical Microbiology and infectious diseases at the University of Manitoba. And...
Now Playing: Radiolab

Dispatch 1: Numbers
In a recent Radiolab group huddle, with coronavirus unraveling around us, the team found themselves grappling with all the numbers connected to COVID-19. Our new found 6 foot bubbles of personal space. Three percent mortality rate (or 1, or 2, or 4). 7,000 cases (now, much much more). So in the wake of that meeting, we reflect on the onslaught of numbers - what they reveal, and what they hide.  Support Radiolab today at Radiolab.org/donate.