Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Malignant bone marrow disease: New hope for MPN patients

05.02.2019

Myeloproliferative neoplasms (MPNs) are still difficult to treat. A team from Vetmeduni Vienna and the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences/Medical University of Vienna has discovered a new therapeutic approach that could fundamentally change this situation, as evidenced by a study that was published recently in the academic journal Blood.

Myeloproliferative neoplasms (MPNs) – a group of rare but malignant bone marrow disorders


MPNs are a group of rare, malignant diseases of the bone marrow involving the production of an excess of red blood cells, white blood cells and/or platelets. MPNs are chronic diseases with only 1 to 2 new cases diagnosed per 100,000 people every year.

MPNs can affect people at any age, but they are most common among adults around 60 years old. Men have a slightly higher risk to develop the disease compared to women.

MPNs are caused by genetic changes (mutations) of the hematopoietic cells in the bone marrow that are acquired spontaneously, due to certain genetic predispositions or as a result of environmental influences. Over 80% of patients with MPNs exhibit an acquired point mutation in the gene JAK2.

This so-called JAK2V617F mutation causes JAK2, a regulator of cell proliferation, to be constantly turned on. As a result, the affected cell begins to divide out of control – and the illness takes its course.

MPN patients have so far been treated with ruxolitinib, a JAK2 inhibitor. Ruxolitinib effectively controls the symptoms but does not offer a cure, as the malignant stem cell clone is located in the bone marrow and is generally not attacked.

Discontinuing the treatment involves a high risk of relapse or progression to AML, a form of leukaemia. Therefore, it is of importance to discover new therapeutic approaches.

Significant factor influencing the disease: the protein CDK6

A research team led by Veronika Sexl from Vetmeduni Vienna and Robert Kralovics from CeMM/Medical University of Vienna succeeded in doing just that. Using a mouse model, they identified the protein CDK6 as an important factor influencing the development of JAK2V617F-initiated MPN.

“We were able to show that in the absence of CDK6, the proliferation of affected stem cells was reduced and cell death was increased. As a consequence, the absence of CDK6 ameliorated the clinical symptoms and increased life expectancy,” says Sexl.

Novel therapeutic approach for MPN patients

The absence of CDK6 clearly attenuates the symptoms in the long term. The spleen, greatly enlarged by the disease, shrinks back to its normal size and the progression of the disease is delayed. Kralovics:

“CDK6 is a central signalling node that connects cell cycle control; the activation of the protein NFκB, a master regulator of inflammation; apoptosis, which refers to the programmed cellular death; and malignant stem-cell function. Our work indicates that fine-tuning the level of CDK6 influences this mechanism and could potentially improve the quality of life of MPN patients. This opens up the possibility of a completely novel therapeutic approach.”

Wissenschaftliche Ansprechpartner:

Barbara Maurer
Institute of Pharmacology and Toxicology
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-2901
barbara.maurer@vetmeduni.ac.at

and

Veronika Sexl
Institute of Pharmacology and Toxicology
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-2910
veronika.sexl@vetmeduni.ac.at

Originalpublikation:

The article “CDK6 coordinates JAK2V617F mutant MPN via NFκB and apoptotic networks” by Iris Z. Uras, Barbara Maurer, Harini Nivarthi, Philipp Jodl, Karoline Kollmann, Michaela Prchal-Murphy, Jelena D. Milosevic Feenstra, Markus Zojer, Sabine Lagger, Reinhard Grausenburger, Beatrice Grabner, Raimund Holly, Anoop Kavirayani, Christoph Bock, Heinz Gisslinger, Peter Valent, Robert Kralovics and Veronika Sexl was published in Blood.

Weitere Informationen:

https://www.vetmeduni.ac.at/en/infoservice/press-releases/press-releases-2019/ma...

Mag. Georg Mair | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Happy hour for time-resolved crystallography
17.09.2019 | Max-Planck-Institut für Struktur und Dynamik der Materie

nachricht Too much of a good thing: overactive immune cells trigger inflammation
16.09.2019 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Happy hour for time-resolved crystallography

Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Hamburg and the European Molecular Biology Laboratory (EMBL) outstation in the city have developed a new method to watch biomolecules at work. This method dramatically simplifies starting enzymatic reactions by mixing a cocktail of small amounts of liquids with protein crystals. Determination of the protein structures at different times after mixing can be assembled into a time-lapse sequence that shows the molecular foundations of biology.

The functions of biomolecules are determined by their motions and structural changes. Yet it is a formidable challenge to understand these dynamic motions.

Im Focus: Modular OLED light strips

At the International Symposium on Automotive Lighting 2019 (ISAL) in Darmstadt from September 23 to 25, 2019, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, a provider of research and development services in the field of organic electronics, will present OLED light strips of any length with additional functionalities for the first time at booth no. 37.

Almost everyone is familiar with light strips for interior design. LED strips are available by the metre in DIY stores around the corner and are just as often...

Im Focus: Tomorrow´s coolants of choice

Scientists assess the potential of magnetic-cooling materials

Later during this century, around 2060, a paradigm shift in global energy consumption is expected: we will spend more energy for cooling than for heating....

Im Focus: The working of a molecular string phone

Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Potsdam (both in Germany) and the University of Toronto (Canada) have pieced together a detailed time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is accomplished via a water-network akin to a string telephone. This communication is aligned with a ‘breathing’ motion, that is the expansion and contraction of the protein.

This time-lapse sequence of structures reveals dynamic motions as a fundamental element in the molecular foundations of biology.

Im Focus: Milestones on the Way to the Nuclear Clock

Two research teams have succeeded simultaneously in measuring the long-sought Thorium nuclear transition, which enables extremely precise nuclear clocks. TU Wien (Vienna) is part of both teams.

If you want to build the most accurate clock in the world, you need something that "ticks" very fast and extremely precise. In an atomic clock, electrons are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Society 5.0: putting humans at the heart of digitalisation

10.09.2019 | Event News

Interspeech 2019 conference: Alexa and Siri in Graz

04.09.2019 | Event News

AI for Laser Technology Conference: optimizing the use of lasers with artificial intelligence

29.08.2019 | Event News

 
Latest News

Novel mechanism of electron scattering in graphene-like 2D materials

17.09.2019 | Materials Sciences

Novel anti-cancer nanomedicine for efficient chemotherapy

17.09.2019 | Health and Medicine

Fungicides as an underestimated hazard for freshwater organisms

17.09.2019 | Ecology, The Environment and Conservation

VideoLinks
Science & Research
Overview of more VideoLinks >>>