Hi @garyr443. Every second, our bone marrow produces several million blood cells. Over a single day, we produce 200 billion red blood cells, 400 billion platelets, and 10 billion white blood cells. Each cell replicating with incredible precision, identical clones of each other. It makes a copy of its DNA and sometimes the copy is not quite perfect. That small difference from the original DNA sequence is a mutation. All it takes is one strand of DNA to misfire in a cell to set the ball rolling for a blood cancer or condition.

We all have cancer cells floating around our body daily. But our immune system is on a mission to seek and destroy these rouge cells. Some of the defects that happen also allow them to go undetected by our immune system. When that happens, those defective cells keep proliferating without an off switch.

Most of the defects have unknown causes as to what triggers the misfire, but there are some strands of DNA more susceptible to mutation than others. From what I learned mutations can happen randomly. There are spontaneous mutations that concur naturally during DNA replication without any external influence. And some through exposures to toxins such as pollution, viral infections which can insert their genetic material into host DNA, causing mutations, ionizing radiation found naturally in our environment, from random gamma rays shooting through the earth, the aging process, etc., all of which may break down healthy DNA. If there’s a weak spot, that’s the first place to misfire.

In your case, you have acquired a mutation on your CALR gene. Mutations on that gene change the protein in a very specific way. They alter the last section of the calreticulin protein, called the C-terminus, the tail end of the protein chain. Every time a cell with that defective DNA splits it creates malignant clones.

The good news is that with continued research, there are new abrogating drugs and targeted therapies being developed which are aimed at molecular remission and eliminating the malignant clones.
I’ve benefited from abrogating drugs myself in my AML (acute myeloid leukemia) odyssey. I have some amazingly brilliant research scientists on my medical team. We’ve discussed my case at length. While there may be theories as to what caused my 3 mutations of AML, there was no precipitating event that could be attributed. But thanks to these targeted drugs, the most aggressive mutation was curtailed.

So the good news for you and others with the CALR mutation is that there are ongoing clinical trials for bispecific antibodies. These are engineered to bind to the mutant CALR while simultaneously engaging a T-cell to destroy the malignant clone.

In fact, right now, our own member @drbart86 is involved in this clinical trial for the CALR mutation! He’s been sharing his journey with us.
https://connect.mayoclinic.org/comment/1607218/
Other areas being explored are:
~Chimeric Antigen Receptor (CAR) T-cell therapy
~Peptide vaccines to train the patient’s immune cells to eliminate cells carrying the CALR
mutation is another area of potential.

While you may never know the exact cause of your mutation there is hope on the horizon that you may not always need the HU. I’m sorry to see the juice experiment was a bust. But thank you for sharing your information with us.

@garyr443 my ET is caused by the same mutation-CALR 9- that you have. My doctor said I was born with it. It just activated when I hit 73. Mutations are weird like that! I started with 1000mgs HU once a day. That was in April. My platelets dropped like a stone! They are now at 256 from 867. My red blood cells have also dropped big time. My white are just hovering above the “too low” level. My CNP lowered my dose to 500mgs once a day, but last blood test showed the platelets still at 256 and a continued fall of my red blood cells. I have an appointment soon and will see what the doctor thinks. I was utterly exhausted before the HU was lowered. The skin under my nails is dark grey to black. I wear nail polish to cover that up! I still feel tired each day, but it isn’t so bad now. I never nap! I eat like I always have and exercise a lot. Everyone is different, so you kind of have to decide what your goal is and how to reach it. You probably don’t want to have a stroke or heart attack from a clot, so that should weigh in as you decide your path forward. There are other drugs besides HU. ET is not well researched yet, so the older drugs used to treat the condition successfully are the ones the doctors like to prescribe. Still, all the feedback on these treatments has to come from us, the patients. So, speak up else how will our doctors know what this is like! I speak up a lot!