Have you ever asked yourself ‘why do I have an MPN?’.
I know I have.
It’s a question that I am sure appears frequently at point of diagnosis and occasionally resurfaces over the course of living with an MPN. The chronic nature of the disease means that patients like us have a long time to think about what might have caused it and whether in hindsight there was anything we could have done differently to avoid this outcome. Similarly, its rarity within the general population raises the question of why we somehow defied the odds and found ourselves members of the MPN community.
The appearance of migraines with aura aged 9, which I’ve written about in previous blog posts, has led me to zoom in on this as a likely moment when my MPN journey began, even though I wasn’t officially diagnosed with ET for another 12 years. I only have one set of previous blood results, taken when I was at school aged 16, which shows I had an elevated platelet count even then. Apart from this lone test, all I have to go off are the date when my symptoms started and the fact they got progressively worse until I started taking Clopidogrel for ET aged 21.
Focusing on 2003, then, the year I started to experience migraines, means my family and I have wracked our brains as to what preceded this date and what else might have been happening around the same time. You might have done this too.
I’ve wondered whether my MPN was sparked by getting two viral infections that year, including swine flu and something called ‘slapped cheek syndrome’ whilst on holiday in Portugal.
My mum has looked back further and asked whether it could have been the multiple scans and operation she had whilst she was pregnant with me.
And my dad has questioned my exposure to chemicals and fertilisers while playing out on the golf course.
In other words, we’ve thought about – and tentatively implicated! – just about everything, and even though it’s perhaps a pointless exercise, searching for the proverbial needle in a haystack, I still find myself mulling over the question of ‘why’ now and again, and thinking about what might have been ‘my’ ET catalyst.
It’s even arisen whilst I’ve been sitting in lectures at university. My ears pricked up when learning about the overlaps between environmental and health geography, and specifically the relationship between place and illness. We came across numerous studies that identified regional clusters of disease and analysed the factors that might explain patterns of sickness in local populations.
You might be familiar with these ideas in the context of environmental justice movements, which challenge the uneven distribution of environmental ‘goods’ and ‘bads’; that is to say, how environmental ills, such as toxic waste dumps or polluting factories, are disproportionately located in poor, politically disenfranchised, and racial minority communities.
A famous example is the so-called ‘Chemical Corridor’ along the Mississippi river in the American state of Louisiana, which is home to one of the highest concentrations of petrochemical infrastructure and records unusually high incidences of disease and ill-health in local communities.
In an article entitled ‘Toxic Space and Time’, Thom Davies (2018, p.1542) – who is an environmental and political geographer now based at the University of Nottingham – notes that “such is the stigma of this industrialised landscape for poor health and increased mortality among its inhabitants that the region is commonly referred to as Cancer Alley”.
This unfortunate label is borne disproportionately by the rural, economically disadvantaged, and predominantly African American communities that live adjacent to the heavily industrialized river, and interestingly, Davies (2018, p.1541) draws attention to the area’s history as the site of former sugar plantations, meaning “many families suffered a toxic inheritance from the historical geographies of slavery”.
The name given to this type of research is ‘toxic geographies’ and it illustrates neatly the relationship between place and health, and how geography can be deeply implicated in questions of disease.
These ideas have been touched on in a few MPN talks that I have attended. Clinicians have pointed to regions in different countries where there are remarkably high numbers of MPN patients; findings which suggest there may be something about that location and its characteristics worth investigating further.
Unsurprisingly, it has made me think about the place where we live.
Our house is built on the site of a former blacksmith’s workshop, a place where skilled craftsmen used to heat and forge different metals.
Our village is home to a wood factory, which involves chemical extraction and treatment.
Similarly, my journey to school passed through a town with a roadside timber factory that meant the air was always thick with the smell of chemicals.
And my dad has reminisced about his childhood, playing in the streams and rivers in Manchester which were tinged with colourful clothing dyes pumped out by the local textile factories.
This is not to suggest any of these examples provide ‘the’ answer or are ‘the’ cause of our MPNs, but they certainly provided me with food for thought when thinking about how the environment can play a part in our health and wellbeing, and perhaps affect our predisposition to genetic mutations and disease.
Finding out the cause – or causes – of MPNs is at the heart of the MOSAICC study (MyelOproliferative neoplasmS: An In-depth Case-Control), which you might have heard about at one of MPN Voice’s patient forums.
Although there have been amazing strides in recent years in identifying genetic mutations associated with MPNs, there is still a gap in knowledge and understanding about the risk factors that might have led to the acquisition and development of these driver mutations.
This is where the MOSAICC study comes in.
It is a collaborative, UK-based research project between Queen’s University Belfast and the University of Aberdeen which aims to gather from newly diagnosed patients and their non-blood relatives or friends qualitative information, like occupation history and lifestyle, and biological samples, such as saliva and toenail clippings (yes, you read that correctly!), to try and piece together possible causes of MPNs.
The study opened to recruitment at the end of 2020, but was – like many things – paused temporarily due to the Covid-19 pandemic. Excitingly, it’s just restarted this month and although it’s likely to be a few years before we find out the results, it’s a really positive step towards knowing more about the origins and contextual factors surrounding MPNs.
Another study – published in the prestigious journal Nature in January 2022 – which caught my eye and tackles the question of why we have MPNs comes from the Wellcome Sanger Institute and University of Cambridge. These researchers performed genomic sequencing of 12 MPN patients between the ages of 20 and 81.
At first, it was the inclusion of this 20 year-old patient that made me sit up and take notice. ‘Yes!’, I thought, ‘someone like me is an integral part of this research’, and was instantly grateful for their participation.
I read on about the team of scientists analysing the patients’ blood samples in remarkable ways: tracing the ancestry of their blood cells, estimating the date when they acquired their gene mutation(s), and tracking how fast the MPN grew in them over time.
Their headline finding stopped me in my tracks.
“In these 12 patients, the first cancer-linked mutations emerged as early as a few weeks after conception and up to age 12, despite cancer symptoms presenting decades later in life”.
I was stunned.
Up until seeing this study, I’d always thought MPNs are caused by environmental factors; a conclusion that I, rightly or wrongly, had taken to mean something I had been exposed to or done had led to my MPN.
But some of the patients in this research had acquired their gene mutation, like JAK2, in utero, meaning there was nothing they could have done differently to avoid acquiring it.
Their next result had the same startling effect on me.
The researchers report that the average length of time between these patients acquiring the JAK2 mutation and presenting clinically with an MPN was 30 years.
Put simply, they acquired their genetic mutation in utero or childhood, but didn’t develop the MPN until decades later.
This study felt – and still feels to me – paradigm shifting.
As the authors reflect in their abstract and conclusion, these results about the lifelong trajectories of MPN origins and development raise questions about, and opportunities for, earlier detection and intervention. This includes whether current or future treatments could be used to slow down or prevent the development of an MPN once a person has been identified as having a driver mutation and is therefore ‘at risk’.
For me, thinking about the MOSAICC study and young patients in particular, it makes me wonder whether researchers in Belfast and Aberdeen will be able to identify common social or environmental factors across patients’ childhoods that might explain why we presented with an MPN in the early, rather than later, stages of our lives. Is there a thread linking us all together that might provide another key into the roots and evolution of MPNs?
So where does this leave us today?
Well, I am optimistic that these examples show we are learning more about MPNs every day, and it’s only a matter of time before there are further breakthroughs in thinking, disease management, and treatment. They reaffirm the importance of patient participation in research and suggest so much can also be learnt by us sharing our stories and experiences in the MPN community.
We might not yet know for certain why we have an MPN, but we’re a lot closer to the answer than we used to be.
If you have any thoughts, ideas, or experiences you’d like to share with Alice on this topic or her previous blog posts, you can contact her by email at: email@example.com
If you’d like to read more about the MOSAICC study and research from the Wellcome Sanger Institute, you can do so at the following links:
You can also download a copy of Thom Davies’ (2018) paper ‘Toxic Space and Time: Slow Violence, Necropolitics, and Petrochemical Pollution’ here: (PDF) Toxic Space and Time: Slow Violence, Necropolitics, and Petrochemical Pollution (researchgate.net)