What do all these words mean? (Part 2)

What does it mean if a person is CD117 positive in a biopsy? Is this bad?

In the context of mast cell disease, it usually just means that mast cells were found.

 

If CD117 is normal for mast cells, why are people sometimes “negative for CD117” on biopsies?

This sometimes happens. When you have mast cell disease, you often have more CD117 receptors on mast cells. This makes it easier for the test to find them. So when you are found to be “negative for CD117” in regards to mast cell disease, you are not truly “negative”. You just express a lower amount of CD117 receptors so the test didn’t see them.

 

I am a mast cell patient and my bone marrow biopsy was positive for CD117. How do I know that it is normal mast cells that show CD117 and not these other dangerous cells you mentioned?

You can tell by looking at the cells with special stains. Pathologists and immunohistochemistry scientists are very skilled at distinguishing one cell type from another. They can tell based upon what the cell looks like in addition to being positive for CD117.

 

If I am CD117 positive in a biopsy, does that mean I am “CKIT positive”?

No. If I could do away with one single phrase in mast cell terminology, it would be CKIT+.

CKIT+ is a term used to mean “positive for the D816V mutation in codon 816 of the CKIT gene”. It means you are positive for a mutation that has been associated with neoplastic disorders of mast cells. So when people say they are CKIT+, they mean they were found to have a mutation. They do NOT mean they were found to have CKIT/CD117 on their mast cell surfaces, because this is totally normal and is the case for everyone.

Additionally, the test to detect CD117 on a cell surface is NOT the same test used to identify the D816V mutation. That test breaks open the cells and looks for a specific mutation in the DNA sequence. They are not run at the same time.

 

Why is it important to know if I am positive for the D816V mutation (CKIT+)?

The D816V mutation changes the shape of the CKIT receptor. Due to this wrong shape, the receptor does not need SCF to bind to the receptor to tell the mast cell to live longer. In this new shape, the receptor is stuck in an “activated” position, so it is telling the cell to live longer all the time, without SCF. This is called “autoactivation”.

The D816V mutation is one of the minor criteria for systemic mastocytosis, so it is important for classification purposes. Also, it may affect your treatment plan in the unlikely situation of needing chemotherapy.

 

What is CD25?

CD25 is part of a receptor for a molecule called IL-2. Normally, mast cells do not express receptors for IL-2, which is a molecule that regulates development of T cells. When mast cells express CD25, it is an indication that the mast cell is neoplastic. Many T cells normally express CD25, so if it is on a biopsy report, keep in mind that it’s abnormal on mast cells, but not everywhere.

Presence of CD25 on mast cells is one of the minor criteria for SM.

 

What is CD2?

CD2 is an example of a “CD” molecule that is not a receptor. It is a cell adhesion molecule so it helps cells stick together. Normally, mast cells do not express CD2. When mast cells express CD2, it is an indication that the mast cell is neoplastic. Many T cells normally express CD25, so if it is on a biopsy report, keep in mind that it’s abnormal on mast cells, but not everywhere. CD2 is a less accurate indication of SM than CD25.

Presence of CD2 on mast cells is one of the minor criteria for SM.

 

What is CD30?

CD30 is a receptor for proteins associated with tumor necrosis factor. It is commonly referred to as a tumor marker, but this is not always the case. CD30 has recently been shown to be frequently positive in patients with all forms of SM (ISM, SSM, SM-AHNMD, ASM). However, on other cells besides mast cells, it may indicate lymphoma or other conditions.

 

What is CD34?

CD34 is another cell adhesion molecule. It is thought to allow stem cells to attach to proteins in the bone marrow. It is found on many progenitor cells, cells that later become other kinds of cells. Mast cells express CD34, though this tends to be lost as they move into tissues.

4 Responses

  1. Robin April 19, 2015 / 8:20 am

    I appreciate the clarity with which you write about mast cell research. I am curious about any research linking mast cell receptors, hashimotos/autoimmune illness and dysautonomia. I am aware that IL-18 and 12 may play a role in the Hashimotos/MCAS connection. Additionally, I believe TRH can be a mast cell degranulator. Is this just a never ending loop? Or does this process involve some type of mast cell receptor abnormality? How close is research to identifying mast cell receptor abnormalities in MCAS?

    Robin

  2. Heather E. January 12, 2016 / 2:00 pm

    I thank you for all of your work in communicating mast cell info to everyone. I greatly appreciate the information presented in a manner I can digest it. Now for my question. I have a 3-yr-old who was diagnosed DCM at 5 mths, and later (age 2) diagnosed SM through a bone marrow biopsy (overseen by the mast cell specialist at NIH). We are part of the pediatric masto NIH study, and they have tested for the mutation. The result is D816Y. I usually see D816V referenced as the “common” mutation with SM. What is the difference between the “V” and the “Y”?

    • Lisa Klimas January 12, 2016 / 10:06 pm

      There are twenty essential amino acids. Your DNA building blocks are called nucleotides. Every three nucleotides (one codon) makes one amino acid. Lots of amino acids together make proteins. This is the central dogma of biology.

      In biology, we abbreviate those essential amino acids to one letter for the ease of transcription. The D816V mutation means that at codon 816, the correct sequence makes the amino acid aspartic acid, abbreviated D. But the mutation changed the sequence so instead of making aspartic acid (D), it made valine (V). D816Y means that instead of making aspartic acid, it made tyrosine (Y). Since I’m sure someone will ask, no, the fact that this was changed to tyrosine has nothing to do with tyrosine kinase inhibitors.

      I did a detailed explanation of D816V here:
      https://www.mastattack.org/2014/06/gene-expression-and-the-d816v-mutation/

      D816V is far and away the most common mutation at codon 816, but the WHO criteria don’t actually say that you need to have the D816V mutation. The criteria say you need to have a mutation at codon 816. This was written this way to accommodate the rarer, but still present, D816Y mutation, as well as allowing for the possibility of other mutations there.

      • Heather E. January 13, 2016 / 10:01 am

        Thank you SO much for your reply. The info on codon 816 helped explain things immensely. Blessings!

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