Myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS)

Myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS)

Myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) are a group of rare blood cancers that are not well known by the general public, but that together are diagnosed in more than 5,000 people in the UK every year. Many more people live with these conditions without being diagnosed.

We have a diverse portfolio of research that is advancing our understanding of MPN and MDS, that could lead to new treatments and improve the way people with these types of blood cancer are cared for.

Myeloproliferative neoplasms (MPN)

Myeloproliferative neoplasms (MPN) - also called myeloproliferative disorders – are diagnosed in over 3,000 people in the UK per year. MPNs includes: polycythaemia vera (PV), essential thrombocythaemia (ET) and myelofibrosis (MF). The three MPNs are distinct blood cancers, but they have one feature in common – they affect the levels of blood cells found in the body.

People with PV produce too many red blood cells, causing the blood to become thicker than normal. ET occurs when there are too many platelets in the blood, which can cause the blood to clot. People with MF have an overactive bone marrow, which develops scar tissue (known as fibrosis). The scar tissue builds up inside the bone marrow and blood cells can’t develop properly causing other complications including anaemia.

MPN usually develops slowly over a number of years, but in some people they can change into acute myeloid leukaemia (AML). Most people diagnosed are over 60, and many have other health problems which can make treatment more difficult. The aim of treatment is usually to control symptoms rather than cure the condition. 

People can be given aspirin, which helps reduce the risk of blood clots; a mild chemotherapy called hydroxycarbamide that stops cancer cells making and repairing DNA; or interferon or anagrelide – both slow down the production of platelets. Many people with MPN have changes in the JAK2 and CALR genes, and drugs that target these changes, such as ruxolitinib, have also been successful. 

Although research has come a long way, MPN is extremely complex - both in biology and genetics. Our researchers are trying to gain a better understanding MPNs so we can improve diagnosis, develop better tools that predict outcome, and design new treatments.

Myelodysplastic syndromes (MDS)

Over 2,000 people are diagnosed with myelodysplastic syndrome (MDS) every year in the UK. 

In MDS, the bone marrow is usually more active than normal, but the cells it produces are not healthy and many die either before they reach the bloodstream or shortly afterwards. This results in the number of blood cells in the bloodstream being reduced, or the circulating cells in the blood do not work as well as they should. MDS varies between people - some have just one type of blood cell that is low, and in others, all types of blood cells are affected. 

In addition to low blood counts, MDS can develop into acute myeloid leukaemia (AML) over time. The risk of this occurring depends on the type of MDS, and some people with early forms of the disease may never progress to AML.

Treatment options for MDS can vary – some people may just need treatment to control their symptoms, but others may need high-intensity treatment such as a stem cell transplant. 

The cause of MDS remains largely unknown.

Our research is looking at how MDS develops, and why some people with MDS go on to develop AML. We are also researching more into rare inherited forms of MDS, and have a trial that is looking at improving the way we treat people living with MDS.

Rare cases of inherited MDS

Most cases of MDS and AML are thought to result from genetic mistakes picked up over a person’s lifetime, but a handful of cases arise because they have inherited genetic faults that increase their likelihood of a cancer developing. These cases represent a special group of people who require a unique management approach; they also provide an excellent opportunity for the identification of the fundamental steps that cause the disease.

We have a major research programme that is studying people with inherited MDS, so we can improve the management of this group of people. 

Improving care for people with inherited forms of MDS

Lead researcher - Professor Inderjeet Dokal, Queen Mary University of London
Myelodysplastic syndromes (MDS)
The biology and management of familial myelodysplasia and leukaemia
By studying people with inherited MDS who are in the same family, Professor Dokal and his team hope to identify the fundamental steps that cause the disease. The team also want to determine the genetic variability of the disease, characterise new genes that drive MDS, and improve the management of people who have these inherited forms of MDS.

Searching for new ways to treat people with MDS

Treatment options for MDS can vary. Some people may just need treatment to control their symptoms, but others may need chemotherapy, or even require a stem cell transplant. 

A recent trial has shown that a chemotherapy called azacitidine improves survival in people with high risk MDS. But many people in this trial had to have their azacitidine reduced or stopped because of low platelet counts and bleeding. We are supporting a trial called ELASTIC that wants to see if adding a drug called eltrombopag helps to keep the platelet count up during azacitidine treatment.

We are also supporting trials that want to reduce the side effects and boost the chances of a successful stem cell transplant, and looking at treatments for people who have relapsed MDS after a stem cell transplant. And we are finding alternative treatments for older people who have high-risk MDS who are unable to tolerate high intensity chemotherapy.

FIGARO trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A randomised trial of the FLAMSA-BU conditioning regimen in patients with acute myeloid leukaemia and myelodysplasia undergoing allogeneic stem cell transplantation
This trial is looking at a reduced intensity conditioning regimen called FLAMSA-BU. Researchers think that this treatment could improve outcomes in older people because of reduced side effects and a lower risk of AML or MDS returning. FLAMSA-BU will be compared with standard intensity conditioning.

VIOLA trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A phase I trial of combined azacitidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia who relapse after allogeneic stem cell transplantation
People with AML or MDS are usually treated with high doses of chemotherapy, followed by a stem cell transplant. But AML and MDS can come back after a transplant, and when it does it becomes much more difficult to treat. Researchers want to know if combining azacitidine and lenalidomide can help this group of people.

RAvVA trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A randomised phase II trial of 5-azacitidine versus 5-azacitidine in combination with vorinostat in patients with relapsed acute myeloid leukaemia ineligible for salvage chemotherapy
In this trial, researchers want to know if azacitidine given with vorinostat is better than azacitidine alone in people with AML or high risk MDS who are unable to tolerate intensive chemotherapy.

PRO-DLI trial

Chief investigator - Dr Victoria Potter, Kings College Hospital, London
Acute myeloid leukaemia (AML) Chronic myelomonocytic leukaemia (CMML) Myelodysplastic syndromes (MDS)
A phase II prospective trial of prophylactic donor lymphocyte infusions for the prevention of relapse post HSCT in patients with high risk myeloid malignancy
Stem cell transplantation may cure acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), but unfortunately people can suffer a relapse after transplant. Researchers want to see if giving white blood cells from the stem cell transplant donor can be used after transplantation to prevent relapse.

What causes MDS to develop into AML, and what can we do to stop it?

Lead researcher - Professor Jacqueline Boultwood, University of Oxford
Myelodysplastic syndromes (MDS)
An investigation of the molecular pathogenesis and pathophysiology of MDS, including the 5q- syndrome: identification of new therapeutic targets
People with myelodysplastic syndromes may go on to develop acute myeloid leukaemia, so Professor Boultwood and her team want to understand this in greater detail. The team will investigate what genetic faults drive the progression of MDS, which could reveal new drug targets.

Developing targeted therapies for MDS

Lead researcher - Professor Sten Eirik Jacobsen, University of Oxford
Myelodysplastic syndromes (MDS)
Unravelling the molecular and therapeutic targets in single del(5q) MDS stem and progenitor cells
In myelodysplastic syndromes (MDS), a small population of cancer stem cells are often left undamaged by currently available therapies, which means the disease can return. These cancer stem cells can also acquire new genetic faults over time, so Professor Jacobsen and his team are investigating these faults with the aim of developing more efficient, targeted MDS therapies.

Testing new treatment options for MPN

After a group of scientists led by Professor Green at Cambridge found that changes in the JAK2 and CALR genes were driving MPN progression, researchers were able to develop drugs that target these changes. Drugs that target these changes, such as ruxolitinib which targets JAK2, have led to significant improvements for people living with MPN. But some people are unable to tolerate the side effects of these treatments, so researchers are looking for new ways to treat MPN.

We are supporting trials that are testing if an already available drug used in breast cancer will work for people who have MPN with the JAK2 and the CALR gene changes, and if ruxolitinib will work in people who have relapsed after receiving chemotherapy. Another trial is testing if two drugs that are usually given alone - chemotherapy and ruxolitinib - can be safely given together.


Chief investigator - Professor Claire Harrison, Guys and St Thomas’ NHS Foundation Trust
Myeloproliferative neoplasms (MPN)
A phase II trial to assess the effects of tamoxifen on the mutant allele burden and disease course in patients with myeloproliferative neoplasms
Researchers want to know if tamoxifen, which is already being used to treat breast cancer, could also help people with myeloproliferative neoplasms (MPN) who have JAK2 and the CALR gene changes. Tamoxifen will be given alongside the standard treatment for MPN.

MAJIC trial

Chief investigator - Professor Claire Harrison, Guys and St Thomas’ NHS Foundation Trust
Myeloproliferative neoplasms (MPN)
A phase II study of ruxolitinib (INCB424) in patients with high risk polycythaemia vera or essential thrombocythaemia resistant to or intolerant of standard therapy
This study is for people with a type of blood disorder called myeloproliferative neoplasms (MPN), which includes polycythaemia vera (PV) and essential thrombocythaemia (ET). Doctors usually treat these blood cancers MPNs with chemotherapy, but treatment isn't suitable for everyone. Researchers think that a drug called ruxolitinib may help people with high risk PV and high risk ET who are unable to have chemotherapy. 

Understanding the genetics and biology of MPN

Our research is identifying new genetic changes that happen in MPN. We also want to explore how these gene changes vary between people, and what influences this variation. This research will improve the way people with MPN are managed, and could lead to new treatments for the disease. 

Mapping the genetic changes in MPN

Lead researcher - Professor Nick Cross, University of Southampton
Myeloproliferative neoplasms (MPN)
The molecular pathogenesis of atypical chronic myeloproliferative neoplasms and related disorders
Using state-of-the-art genomic technologies, Professor Cross and his team are identifying new genetic changes in MPNs. They will see what impact these genetic changes have within the biology of MPN, and also how this manifests itself clinically. The information will be used to develop new diagnostic and therapeutic strategies for people living with MPN.

Understanding the biology of MPN to improve patient care

Lead researcher - Professor Anthony Green, University of Cambridge
Myeloproliferative neoplasms (MPN)
The myeloproliferative neoplasms - from molecular mechanisms to improved patient management
Professor Green and his team are focussing on understanding the complex biology of MPNs, and translating their insights into improving patient care. Research will help refine how we diagnose MPN and predict outcome, and also could lead to the development of new therapies.

Taking back control of healthy blood production

Lead researcher - Professor Jon Frampton, University of Birmingham
Myeloproliferative neoplasms (MPN) Myelodysplastic syndromes (MDS)
Effects of inherited MYB deficiency on haematopoietic stem cell function and response to ageing
Professor Frampton and his team are looking at a protein that is involved in leukaemia, myeloproliferative neoplasms, and myelodysplastic syndromes. Some people have lower levels of this protein than others, and researchers want to know if this makes these people more prone to white blood cell diseases. If successful, their work will help in the development of new ways to screen people for these diseases and could lead to new treatments.

What is driving the progression of MDS?

As with most cancers, people with MDS pick up genetic faults over time. One of our research projects is mapping out the time-ordered sequence of genetic faults acquired by people with deficient blood cell production – including aplastic anaemias (AA) and MDS – and how the immune system shapes this. This will not only reveal how and why some AA and MDS cases develop into more aggressive diseases, but also guide therapies to block the disease by manipulating the immune environment.


Do bacterial infections make MDS and AML worse?

Lead researcher - Professor Chris Bunce, University of Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
Human and bacterial NDPKs as novel activators of the NLRP3 inflammasome: Implications for the biology and management of AML and MDS
People with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) often have severe and sometimes life-threatening infections. Professor Bunce and his team are investigating whether these infections are making the cancer worse by causing resistance to drugs and helping the cancer progress. If this is the case, their findings will have major implications for how MDS and AML are treated and managed.

When MDS transforms into acute myeloid leukaemia (AML)

MDS has a risk of transforming into acute myeloid leukaemia, and when this happens, people have limited treatment options. Our research wants to understand why some people progress, and the underlying mechanisms behind this. 

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