Phylogenetic reconstruction of myeloproliferative neoplasm reveals very early origins and lifelong evolution

[Manouche]

« The mean latency between JAK2V617F acquisition and clinical presentation was 31 years (range 12-54 years). Rates of clonal expansion varied substantially (<10% to >200% expansion/year), were affected by additional driver mutations, and predicted latency to clinical presentation. Driver mutations and rates of expansion would have been detectable in blood one to four decades before clinical presentation. This study reveals how driver mutation acquisition very early in life with life-long growth and evolution drive adult blood cancer, providing opportunities for early detection and intervention, and a new paradigm for cancer development. »

biorxiv.org/content/10.1101...

[EmeraldA]

This is very interesting again. Thank you for posting. So basically we have had this most of our lives.

[Aneliv9]

Thank you very much Very interesting and also a bit concerning!

A maybe silly question: does this mean that if a "possible positive Jak2 MPN baby" had blood tests for the detection of jak2 mutation, this test would come back positive? (Sorry i can't find the right words for making a good sentence in English )!!!

[Bigcheat]

Thanks Manouche,

Top article posted by you, once again! This sentence blew me away: ”Concurrent potential exposures during life included smoking, obesity, infections (eg hepatitis C, mumps and whooping cough) and pregnancy.”

Reason being, I was quite ill during 15-16 years of age, having both mumps AND whooping cough back to back. Both were diagnosed in hospital, as well as bone marrow aspirate showing ”abnormal but non-malignant” lymphocytes shortly after at age 18. Doctor mentioned possibility of EBV onset CFS, since I was really tired for year or two. I bet smoking didn’t help either the situation

I have long tried to find some reference that EBV could onset MPN. All doctors have dismissed my EBV theory, and this was the first source to confirm that EBV may indeed have caused my JAK2 mutation almost 30 years before ET diagnosis.

Keep them coming, good work!

Bigcheat

[Chaz1]

Thanks for sharing, I saw this on twitter a few minutes ago because Anna Godfrey & Jyoti Nangalia are hubby's consultants. Jyoti tweets a lot of really good context & also answers people's queries.

We wonder whether hubby's samples were used as he gives regular samples for research.

Despite his initial hesitation at going for a second opinion 2 and a half years ago, being under research consultants instills him with confidence.

[Wyebird]

Thank you, I wondered if my MPN was related to living very close to a substation. That article suggests not.

[Wyebird]

Just an after thought - if what I’ve read is accurate, how is it that the blood sample taken from me and stored 10 years earlier for breast cancer research did not reveal anything.

- I’m under a leading specialist. Through the specialist’s contact, it was brought out of storage to look for early signs. Non existed.

[jointpain in reply to Wyebird]

Do you know what evidence could have been found in a blood test sample from ten years ago that would suggest an mpn or jak2 mutation?

[Wyebird in reply to jointpain]

Hi, I had a stroke 10 years before MPN diagnosis. My specialist was curious. Was the stroke related to my ET? Apparently your platelets don’t necessarily have to be high to have ET there are exceptions. They specifically looked for I think, the mutated gene ( calr).

[Manouche in reply to Wyebird]

The reason could be the lack of sensitivity of the test used for your blood sample (0.1% instead of 0.01%).

« The period of doubling of the pooled data was found as 1.4 years (CI: 1.2 to 1.7 years). This implies that the allele burden grows from 0.01% to 1% in 9.3 years »

mdpi.com/2072-6694/12/8/211...

[Bluetop in reply to Manouche]

Another good one. Thanks so much for posting these.

[Wyebird]

Hi, I had a stroke 10 years before MPN diagnosis. My specialist was curious. Was the stroke related to my ET? Apparently your platelets don’t necessarily have to be high to have ET there are exceptions. They specifically looked for I think, the mutated gene ( calr).

[MCW22]

If I'm reading this correctly it would appear to support what I have always suspected, that my exposure to passive smoking from conception to the age of 25 when I finally lived in a smoke free environment is the cause of my Jak2 + it's the only thing I can think of that would have exposed me to benzene, which we know causes the mutation. I put my theory to one of my consultants a long time ago and she said there was no way of finding out if that was the cause, but she did make a note of it in her letter to my Gp

Carol

[clubdino in reply to MCW22]

Hmm interesting. I was diagnosed at 27...probably had it longer...my mom smoked during pregnancy as well. But I am CALR positive...not sure if that matters but benzene exposure is benzene exposure. I also had to deal with the hardcore indoor smoking. I hated it so much that when I was 8 years old I wrote a editorial to a newspaper about how much I hated second hand smoke and I got it published. Thanks mom.

[MCW22 in reply to clubdino]

Yes it was very 'foggy'in my parents home and food tasted of cigarettes and clothes smelled of them. Paintwork was yellow and house plants didn't survive. Even after I left home any family member who went to visit came back smelling of cigarettes and boxes of chocolates, biscuits etc that we got as presents were inedible. All of this is why I've never smoked a single cigarette in my life.

Carol

[JT_Marlin]

Great article Manouche. Wyebird, I’m in the same boat. I had a heart attack 4 years ago at age 36. Docs couldnt determine the cause and assumed it was a vasospasm which I still meds for today. My hematologist is more convinced that it was the PV though at that time all my blood numbers were in line. So the thinking is that the PV can express itself through thrombotic events even if your blood numbers are well behaved.

Side note, I too grew up w a stepfather who was a serial chainsmoker. I always hated it (and him quite frankly) but perhaps he is the culprit for my PV - he gets the last laugh from the grave (died of lung cancer shockingly several years ago).

[Manouche in reply to JT_Marlin]

It’s possible to have a normal blood count and still get a cardiovascular accident. Blood can be quantitatively ok but qualitatively deficient. Unfortunately, the quality of blood cells or arterial walls is not something haemos know how to manage or diagnose.

[Bluetop]

Very interesting. Thanks for posting.

[rebeccaxxx]

Wow, so am I right in thinking they can test us all and find out how rapidly it is progressing with basic blood tests? Interesting.