International review series on MPNs published

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The April 2025 edition of Haematologica features an excellent review series on MPNs.

The authors of the introduction paper to the series, Australia’s Drs Steven Lane and Yin Yuan, explain that ‘the review series is not designed to be a definitive review of all aspects of MPN biology and treatment. Rather, we have selected a few key topics of particular interest to the field that have been informed by recent advances in basic or clinical research’.

In addition to the paper from Drs Steven Lane and Yin Yuan, paper no 4, ‘Pathogenesis and management of high molecular risk myeloproliferative neoplasms’ also features two Australian coauthors, haematologist and researcher Dr Victoria Ling and researcher Dr Megan Bywater.

The papers are all free to access and linked below:

  1. Prevention, diagnosis and management of myeloproliferative neoplasms: an introduction to a review series,
  2. Evolution of myeloproliferative neoplasms from normal blood stem cells,
  3. ‘Clinical and laboratory approaches to target and eradicate early disease-initiating stem cells’:
    Paper is titled New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-a alter the natural history of the disease?,
  4. Pathogenesis and management of high molecular risk myeloproliferative neoplasms,
  5. ‘Strategies to prevent or treat the devastating clinical consequence of AML arising from antecedent MPN, also known as blast-phase MPN’. Paper is titled Prevention and treatment of transformation of myeloproliferative neoplasms to acute myeloid leukemia.

 

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ASH 2024 overview podcast from Claire Harrison from the UK

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Haematologist Claire Harrison from Guys and St Thomas’ Hospital in the UK is one of the world’s leading MPN experts.

In this podcast she provides an overview of some of the MPN presentations from the American Society of Hematology meeting (ASH) in December 2024.

Yet again, the amount of research into MPNs here in Australia and world-wide is extremely reassuring for patients.

The podcast can be accessed HERE.

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February 2025 MPN Education Foundation patient conference videos

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Every two years the MPN Education Foundation hosts a wonderful patient conference in Scottsdale Arizona, with some of the most distinguished MPN expert presenters. The conference is titled the Joyce Niblack Memorial Conference, and is hosted by the Mayo Clinic.

We are very fortunate to be able to view the conference video presentations and slides.

Here is a list of presenters and topics:

Jyoti Nangalia – MPN Molecular Biology

Rupali Bhave -Managing ET in 2025

Raajit Rampal – Managing PV in 2025

Naveen Pemmaraju – Managing ET in 2025

Ruben Mesa – Guidelines & Gaps in MPN

Jeanne Palmer – Transplants in MPN for 2025

Marina Kremyanskaya – New Drugs for PV

John Mascarenhas – New Drugs for MF

Angela Fleischman – Nutrition & Complementary Approaches for MPNs

Jean-Jacques Kiladjian – Long Term Outcomes of Interferon in MPNS

Steffen Koschmieder – Inflammation in MPNs

Susan Leclair – Learning about my Labs: An MPN Patient Guide

 

 

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New Australian research into causes of thrombosis in MPNs

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The MPN AA is delighted to report on some very recent Australian MPN research into causes of thrombosis in MPNs and, in particular, polycythemia vera (PV).
As MPN patients are aware, MPNs are associated with an increased risk of thrombosis. This Australian research has added a new insight into the mechanism underlying thrombosis which can be such a risk for MPN patients, especially PV patients.

This research was presented at the December 2024 American Society of Hematology (ASH) meeting by haematologist and researcher, Dr Indu Raman. The research was undertaken by Dr Indu Raman, Dr Cavan Bennett, and colleagues at Walter and Eliza Hall Institute of Medical Research, Melbourne, Molecular Oncology and Cancer Immunology, Epworth Healthcare, and Royal Melbourne Hospital.

 

The poster presentation and accompanying paper are titled: Dysregulated Complement Activation in Polycythemia Vera: A Novel Mechanism for Thrombosis in Myeloproliferative Neoplasms Uncovered By Proteomic Analysis

Full poster available for download

While research has identified factors such as increased activation of platelets, neutrophils and elevated expression of molecules directly involved in clot formation, underlying mechanisms of thrombosis are not fully understood. This study aimed to investigate potential mechanisms underlying the increased thrombotic risk in MPNs. This was done through mass spectrometry-based proteomic analysis of bone marrow trephines.

To provide some definitions before reading on:
–  Bone marrow trephines are the solid cores of bone marrow tissue recovered from a patient during a bone marrow biopsy.
–  Proteomic analysis is the analysis of the entire set of proteins that is expressed by a genome, that is the genetic information contained in the cells in that bone marrow sample
–  Complement proteins are a group of immune system proteins – some of many identifiable from the proteomic analysis.

Experiments undertaken by Dr Raman and the research team suggest increased activation of complement proteins, a group of immune system proteins. Overactivation of complement proteins can enhance both inflammation and clot formation.

These findings are novel and have not been well described previously. Dysregulated complement protein activation may contribute to the heightened clotting and inflammation observed in PV.

Dr Raman and team advise that further studies are needed to confirm this finding, which may lead to alternative therapeutic options.

Further detail about the research is available via the ASH Abstract

If you have specific questions for Dr Raman or Dr Cavan Bennett, about this research please first contact the MPNAA at mpnaa@mpnallianceaustralia.org.au

The MPN AA thanks Drs Raman, Bennett and the research team for this important research.

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2024 ASH MPN highlights with Dr Ruben Mesa

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Courtesy of Ann Brazeau of MPN Advocacy and Education International, here is a wonderful summary video of the MPN highlights from the December 2024 American Society of Haematology (ASH) meeting provided by Dr Ruben Mesa.

Watch the video HERE

 

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Patients with CalR mutation – promising ASH update

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The American Society of Hematology’s December 2024 conference included developments in treatments for MPN patients with the CalR mutation. A range of Australian and international immunotherapy research is underway and some treatments are already in clinical trials. It is too early to present results.

A fascinating video about CalR treatment research is linked below.
In the video, Drs Alex Rampotas and Zoë Wong explain that there are already specific immunotherapies being trialled against the CalR mutation, all of which may well be effective.  They specifically mention a ‘B specific T cell engager’ and ‘a blocking antibody against it’.

However their collaboration is about a third type of immunotherapy option, a novel second generation CAR-T cell therapy. They advise that CAR-T is the ‘strongest immunotherapy so potentially  ……. able to overcome some of the immune suppression of myelofibrosis and directly eliminate the malignant stell cells.’

The full video is 8 minutes long, unfortunately with background noise.  However if you have the CalR mutation, watching the video will give you a Christmas present of great promise!

https://www.vjhemonc.com/video/qsoln_mbhbk-development-and-evaluation-of-a-first-in-class-car-t-therapy-against-calreticulin-mutant-neoplasms/

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MPN Horizons meeting 6-8 September 2024 Warsaw – A personal reflection from Sharon MacIntyre

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Well let’s just say it was an honour to attend the MPN Horizons conference this year.  There was representation from MPN specialists, many MPN advocacy groups, PV, ET & MF patients, pharmaceutical companies and more!  The title “Shifting the treatment paradigms of MPN” was very apt. Since I first attended in 2017, sponsors have grown from 3 to now 11! And patient advocacy groups now include Thailand, Korea, and other nations which previously were not represented.  It is such a growing global family to address MPN needs.

The almost 70 participants in Warsaw, Poland were from an amazingly geographically spread of 26 countries, including Australia, India, Chile, to Europe, America and Asia! All were very vocal in sharing new developments for MPN from research to trials, to advocacy and patient stories. All sharing a key purpose – to make life better for MPN patients.

Before we dived into a massive 3 day program, it was refreshing to attend a breakfast session where Pharma was the lead and seemed genuinely keen to collaborate and bridge the access barrier different countries and patients in need have. The session was called “Navigating the Path to Equal and Equitable Care” to discuss the most important barriers for MPN patients.  I learnt a lot, particularly helpful that there is a special consideration element to access which can be sought with the Pharma company directly for review/access to medications.

This was the third time I have attended Horizons and as a highlight for myself being diagnosed at 18 years of age. I was particularly impressed with the inclusion of a session solely for young MPN patients by Alice Watson from UK. Under the auspices of MPN Voice she has started a group for under 40’s MPN patients to ask questions, address issues such as study/work life balance, starting a family and pregnancy, long term MPN and progression.

The sessions from world leading specialists were very informative.  Dr Claire Harrison spoke on state-of-the-art news for Myelofibrosis – including the new prognostic model; how there are more options available for lower risk MF patients; and how the success of Haplo transpants as an option could be explored. A haematologist from Germany, Dr Susanne Isfort, talked about the 3 common MPNs and the drugs she typically uses to treat them, and about data showing that interferon in young patients may be looked at as an option to stop MF progression.

Jon Mattias from MPN Voice presented a session on a great new application “Health Unlocked” which is in development. This app tracks patient symptoms and data that hopefully could be useful for medical appointments and could be integrated into a wearable device.  This type of app could be rolled out globally – but more needs to happen on 3rd party permissions and how to protect personal data.

Dr David Ross from Adelaide Australia, spoke on the differences in an individual’s height and gender etc which often isn’t taken into consideration in treating patients. For example, spleen size, depth and volume in a female 5’2 and a man 6’2 can be completely different in what is considered large! He felt spleen volume is more important than just length – something I had never heard of before. There were pictures from Dr Wendy Erber’s lab in Western Australia on machine learning for precise fibrosis scoring which was very interesting.

Elena Greschner from Austria talked about fatigue and how around 80% of MPN patients suffer fatigue.  Yet only about 30% of haematologists ask their patients about fatigue. She stressed the fact that Quality of Life is important (as well as the blood cell numbers). Dr Patrick Harrington mentioned patient data in his MPN research that showed a fifth of MPN patients can only work reduced hours or need to stop work early before retirement age.  Emphasis was placed on being aware of increased clotting risk, infection and organ failure.

Another brilliant session I thought was valuable were the regional breakouts. Being an MPN AA advocate from Australia – ideas for more Asia/Pacific collaboration were bounced around and very positive. I’m looking forward to seeing some of these ideas come to fruition. Perhaps “Chai for Cancer” events at workplaces in Australia borrowed from advocacy group ‘Friends of Max’ in India’s success.

One of the advocates talked about their “March for Cancer” event and how citizen participation was important!  Perhaps we can bring back a lantern walk for MPN and other blood cancer advocacy.  The kids love this!

The importance of a healthy diet and exercise were again highlighted.  I for one will be trying to implement when my symptoms are ok, a more Mediterranean Diet of real foods (hopefully more than packaged and takeaway) and some gentle exercise for 30 mins a few times a week.

All in all the MPN Horizons conference was absolutely brilliant! A wonderfully informative and collaborative 3 days in Warsaw. I’m looking forward to seeing these developments turn into new application and drugs (some in clinical trials already) and much more positive patient outcomes for the future.

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Inflammation and MPNs

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This presentation by MPN specialist Dr Hans Hasselbalch from Denmark is of great interest to MPN patients.
Whilst the topic is inflammation, and the importance of reducing inflammation, Dr Hasselbalch’s talk is comprehensive.

He explains the latest MPN research findings, including the extraordinary discovery that 11.3% of stroke victims have the Jak2 mutation. He also reminds us of the huge numbers of undiagnosed MPN patients around the world and the possibility of targeting and eliminating the Jak2 mutation when it is in its early CHIP stage.
He explains about the risk of inflammatory bowel disease in MPN patients, the benefit of early intervention with interferon and even a potential role for statins for MPN patients, and so very much more.

His talk is available HERE.

 

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MPN AA CALR research fellowship report

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Young myelofibrosis patient Sarah Gardner* raised a large sum of money for MPN research. Thanks to her brilliant fundraising, the MPN AA was able to fund a fellowship for Dr Chloe Thompson-Peach at the South Australian Health and Medical Research Institute.
The research focuses on the CALR mutation and it is extremely promising.


Image: Dr Chloe Thompson-Peach from SAHMRI

Chloe’s report from the fellowship follows.

Lay Report by Dr. Chloe Thompson-Peach, fellowship recipient

Myelofibrosis is an insidious condition of the bone marrow, which disrupts the normal production of blood cells. It is characterised by painful inflammation, low blood counts and fibrous tissue building up in the bone marrow. In some patients, myelofibrosis can also develop into acute leukaemia over time. The lack of effective therapeutic options for these cancers has led us to the development of a new immune treatment for these individuals.

We have developed a novel immune treatment, a biological therapy, that is a monoclonal antibody directed against the mutant CALR gene, which is the second most common cause of myelofibrosis or essential thrombocythemia.

We have shown this to be effective in cell lines and patient cells harbouring pathogenic CALR mutations in the laboratory.
Additionally, our treatment has also been shown to have no effect on cell lines and patient cells that do not carry mutations within the CALR gene, suggesting it is truly selective, which means it will not have side effects.

This was published recently in a major European science journal, EMBO Reports.

EXCITING UPDATE:

We have recently developed a new version of our antibody which is able to be used in humans without being rejected (called antibody humanisation) and demonstrated that the antibody is still effective at eliminating mutant CALR cells, while leaving healthy normal cells unharmed. We have shown that our antibody is able to significantly reduce the live burden of disease, with mutant cells being completely eradicated in pre-clinical in vivo experiments.

Our antibody reduced the number and size of megakaryocytes formed in CALR mutant patient samples in the lab, a key cell in driving myelofibrosis.

Additionally, we have shown that this antibody can be combined with Jakafi (ruxolitinib) to completely eradicate mutant CALR cells in the lab and re-sensitise cells that are resistant to ruxolitinib therapy alone.

Importantly, our human antibody has shown no signs of toxicity in mice and is in the process of preparation for clinical trial in the near future.

The good news is we have worked out which parts of the mutant CALR protein that causes myelofibrosis can be blocked by the antibody and it looks like we have another antibody that also has activity. We are now using the molecular information we have gained from these antibodies to build new cell therapies (CAR T cell or NK therapies or “bispecific T cell engager” antibodies).

We are hopeful that our research can build a suite of therapies, either to be used on their own or in combination with Jakafi, that will be effective and help move towards demonstration of long-term remission or cure in patients with myelofibrosis, as well as in patients that relapse after a stem cell transplant.

Some of our data was presented at the recent “New Directions in Leukaemia” conference organised by my supervisor Dr Dan Thomas at the University of Adelaide and Stanford University and is under review at a major international journal.

Please stay tuned and thank you for being committed to changing outcomes for patients with MPNs!

*Sarah Gardner’s story is available HERE.

 

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Important new study – high WCC as risk factor for blood clots in PV

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REVEAL study

Findings from an important new study for the management of polycythemia (PV) patients have just been released.

Called the REVEAL study*, it shows that leukocytosis (a high white cell count) is a risk factor for thrombosis (blood clots) in patients with PV. The study showed thrombosis to occur in high and low-risk patients, and even in patients in whom hematocrit was adequately controlled.

To date, known risk factors for thrombosis in PV patients included advanced age, previous history of blood clots, and elevated hematocrit >.45. There was insufficient data to include elevated white blood cell (WBC) counts as a known risk factor.

However, in an analysis of 2271 PV patients, the REVEAL study found 142 blood clots in 106 patients.
Specifically. during the study period of just under 4 years, it identified:

  • Significant associations with initial blood clot occurrence for hematocrit level >45% and WBCs >11 × 109/L .
  • Elevated WBC count was significantly associated with initial thrombosis in both low and high-risk PV patients.
  • Even when hematocrit was controlled at 45% or lower, WBC count >12 × 109/L was significantly associated with thrombosis.
  • There are different risk factors for arterial and venous thrombosis, an observation that has also been reported in essential thrombocythemia. Both leukocytosis and thrombocytosis (high platelet count), poor hematocrit control, and age were associated with a higher risk of arterial thrombosis, whereas female sex, history of previous thrombosis, and leukocytosis turned out to be the main risk factors for venous thrombosis.

The study’s authors feel that, even without a large study proving that lowering leukocytosis reduces blood clots, there is sufficient evidence to ‘support the inclusion of leukocytosis in the definition of high-risk polycythemia vera’. They also suggest that two elements of clinical practice could be changed:
– ‘low-risk patients with persistent leukocytosis could be elevated to the high-risk category and, therefore, be candidates for cytoreduction’ and
– ‘normalization of leukocytes should be included as an objective of treatment in patients receiving cytoreduction.’

There are two abstracts available discussing the REVEAL study’s findings.

REVEAL puts leukocytes into risk stratification 

Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL

* REVEAL is a prospective observational study that enrolled 2510 patients with PV, with median follow-up of 44.7 months (range, 2-59 months). REVEAL stands for The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices.

 

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