Mpl mutation

[Cookiebaker]

I got results from genetic testing for ET and my mutation is mpl . I know this is the rarest of the three mutations and it is the one that most often morphs to myelofibrosis . What else can anyone else tell me about it? I want to find out as much as I can . My sister passed from MF 9 years ago before they knew of this mutation so I don’t know if she had it too. Thank you.

[mjfin72]

Hi Cookiebaker. I have ET diagnosed in 2016 and also have the mpl gene however I did not know that having this gene could be more likely to transition to MF. All I was told was that it was the rarer of the three mutations but treatment plan would be the same.

I have been on Hydroxy since last Feb and responding well to treatment bar a few blips along the way. Would be interested to know more about the likelihood of transition with our gene mutation.

So sorry to hear about your sister. I'm sure having someone close pass away with MF causes you to worry more.

Regards

Mandy

[Cookiebaker in reply to mjfin72]

I do worry about the future after being with my sister so much during her illness and death. Thank you for writing.

[Paul123456]

I’ve not seen any research to indicate that MPL has an inferior prognosis to JAK2. Last research I saw stated similar life expectancy. Hence perhaps you can clarify with your Hem on your next visit. I can send you link to research.

CALR Type 1 has best prognosis but perversely, does increase risk of progression to MF. However very slow progression thereafter.

Best Paul

[Cookiebaker in reply to Paul123456]

My doctor gave me a copy of study that was published in Blood Cancer Journal . There were 665 ET patients in the study. The transformation rate to MF was 33% with driver mutation of MPL compared to 11% in triple negative, 15%Jak2and 21% CALR.

It doesn’t say anything about life expectancy in this article.

Thank you for writing. I enjoy reading about what others know about this disease.

[Paul123456 in reply to Cookiebaker]

This is the link I was referring to

ncbi.nlm.nih.gov/pmc/articl...

Best

Paul

[Paul123456 in reply to Paul123456]

See page 11

‘Although the prognostic models for PMF currently used in clinical practice are essentially based on clinical and hematologic parameters, recent observations indicate that the driver mutation has an independent effect on overall survival and risk of leukemic transformation.16,84,85 In our study of 617 PMF patients, median overall survival was 17.7 years in CALR-mutated, 9.2 years in JAK2-mutated, 9.1 years in MPL-mutated, and 3.2 years in triple-negative patients (Figure 4A). Notably, triple-negative patients had much higher incidence of leukemic transformation compared with either CALR-mutated or JAK2-mutated patients.’

Remember this data is very historic, new treatments will enhance prognosis. Plus a median including older patients with higher rates of progression

[Cookiebaker in reply to Paul123456]

Very interesting Paul. Thank you so much for the link and sharing.

[Tico in reply to Paul123456]

Hi paul,i agree a lot of the data is historical and new treatments will enhance the prognosis along with new discoveries and more knowledge.thank you. Atb, tina.🤗

[TTA_ in reply to Cookiebaker]

I know exactly which study your hematologist gave you, or at least one of them.I probably should post a debunking of the statistics of that study as it is so misleading.

If I am not wrong, the sample of MPL mutated people in that series of studies is under 20 in one study and 32 in another. The samples for other mutations are about 100-200 for CALR and ~400 for JAK2. This alone should have made the types of comparisons they wanted to do lose power.

Then, if I remember correctly, their MPL sample is on average 10 years older than JAK2 and CALR. And in terms of sex of patients, it is the inverse of JAK2 and CALR: ~70% of the MPL sample was male versus ~30% of the other two samples (JAK2 and CALR) were male.

They were comparing apples with oranges there. Older age and male sex are independent risk factors on myelofibrosis. If you group them together and then you also have a very small group, it is difficult to draw any conclusions.

That study cannot statistically tell you anything about your risk of MF progression, not based on their MPL samples.

I hope this helps you.

I have a rare non-canonical MPL mutation and I read so many nonsense studies with speculations it is becoming exhausting.

You can send me the link to the study your doctor gave you, just to compare notes.

[Aime]

Hi, I think it’s also important to remember we are all individuals with probably unique medical histories so just because one person has not survived as long, does not mean another will be the same.

Sorry to hear about your sister, sending E hugs to you. Kindest regards Aime xx😺

[Wyebird]

Hi Cookie,

Your head must still be whirling with information and emotional termoil. I wish you well. Reading your post has enlightened my knowledge.

1- I’ve never heard of MPL mutated gene and I’ve been to lots of MPN forums. I’m CalrET.

2- I thought that Calr had the best prognosis but after reading the posts below it seems it’s the one most likely to transform if you are on hu.

3- if you’ve the MPL gene what do you have, ET, PV or MF?

[Cookiebaker in reply to Wyebird]

Hi Wyebird, I have ET. Hope that it stays ET for a long time. I am 70 and have had high platelets for 4 years. I had just been on baby aspirin until 6weeks ago when platelets reached nearly a million. In the 6weeks of Hydroxyuea they have dropped to 636 with a dose of 500 a day. So good results. I am trying to stay positive... but find myself thinking of my sister and her MF.

[Wyebird in reply to Cookiebaker]

Meds for MF seem to be developing all the time. Watching your sister suffer must have been a double wammy. I wish you well.

[Cookiebaker in reply to Wyebird]

Thank you Wyebird .

[Indigo42916]

Just saw this, and I am ET and MPL, and I understand the chance of progression to myelofibrosis about 30%. I am doing very well on Pegasys, platelets down from high 600's to 200's and feeling great. Good studies on Pegasys and normalizing bone marrow. My rbc's remain high normal and being watched.

Take good care.

[Cookiebaker in reply to Indigo42916]

Hi Indigo, I have a 4month check up next week. My rbc wbc are both below normal. I take Hydroxyurea. I will watch for your posts since you have the same mutation as I do. Thank you for writing.

Cookiebaker

[TTA_ in reply to Indigo42916]

As we are very few with MPL mutation, and as people are often left undiagnosed, the samples used in studies are too small to be reliable in terms of transformation.

Less than a decade ago there were MPN specialists who advised not to test for MPL mutation, they saw it as irrelevant, so there might be a good chunk of MPL mutated people who are assigned as triple negative MPNs. That was an arrogant move in hindsight, as it made the collection of adequate data on MPL more difficult and it left us with the very small and often biased samples we have today.

Who knows, if all people who had MPL mutation were diagnosed adequately, maybe we would learn that MPL is not increasing progression more than other mutations.

[Indigo42916]

Likewise, thanks for sharing, the MPL's are a small lot, not much data for us.

[Indigo42916]

Hi Cookiebaker,

Just wanted to check in and see how you are doing.

Hope all is well.

[Cookiebaker in reply to Indigo42916]

I am doing fine . How about you?

[Indigo42916 in reply to Cookiebaker]

Sorry for the very late reply, doing well had the flu, but got through it. Energy is slowly coming back. Hope all is well with you.

[TTA_]

I am sorry to hear about your sister. My dad also passed away from high-risk myelofibrosis, undiagnosed until after he passed away.We are very different in our illness, even from people with whom we are related and with whom we might share pathogenic mutations. ET can be due to sporadic mutations (you acquired the mutation during your lifetime) or germline (you inherited the mutation from your parents). Most ET cases are due to sporadic mutations. Sometimes, people in a family might inherit not the mutation itself, but the propensity to acquire a pathogenic mutation. This means that two people with ET/MPNs in the same family might have different mutations.

I can imagine how difficult it must be to have to process losing your sister at the same time with having a diagnosis from the same family of illnesses that took her life. I had to pass through this myself. I hope you have people around you who can support you.

Given that this seems to run in your family, did your doctor check whether your mutation might be inherited? Or whether this illness is familial?

Did they give you the information about the name of the mutation?

I have an inherited MPL mutation, MPL R102C, it is non-canonical loss-of-function MPL mutation. I inherited it from my dad.

I will append a couple of studies in the hope they will give you more information. Also, I checked the studies on MPL and risk for MF transformation and those studies have such small samples, I wouldn't consider them relevant. Did you also have a bone marrow biopsy for your diagnosis?

These are several studies for more insight:

pubmed.ncbi.nlm.nih.gov/325...

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...