The difference between CD117+ and CKIT+

Hey, everyone –

I received a request to clarify the difference between being CD117+ and CKIT+.

CD117 is a receptor on the outside of mast cells. It is normal and all mast cells are CD117+. This is how we identify them as mast cells. If you have a bone marrow biopsy done and it says no CD117 is found, this is not because there are no mast cells there. It is because the test for CD117 isn’t sensitive enough to find those few mast cells. This is called the limit of detection (LoD).

When there is more of something present, it is easier to find it. Say I am in a field and there are five tennis balls scattered. If I walk around for a long time, maybe I will find three tennis balls. But if there is only one tennis ball to be found, I may not find it. I have less of a chance of finding it because there aren’t as many so it’s harder.

Being CD117+ is NORMAL for mast cells. It just means that it’s a mast cell. But mast cells that are constantly activated have more CD117+ on their outside membranes. Think of it like the tennis balls – if there are five CD117 receptors on a mast cell, it’s easier for the test to find one. If there is only one, the test might miss it.

CD117 is also called the CKIT receptor. It is a receptor that gives mast cells the signal to stay alive and encourage more mast cells to mature. If you get a biopsy report back and it is CD117+, then it will say CD117. The reason the report doesn’t call it positive for CKIT is historical and has to do with the fact that it was identified first as CD117 and later called CKIT because of similarities with other proteins of similar names.

When mast cell patients say CKIT+, it is a misnomer. It means that they are positive for the D816V mutation in CKIT, which is a marker for systemic mastocytosis. So being CD117+ and CKIT+ are not the same. CD117+ just means mast cell. CKIT+ (D816V) means neoplastic mast cell.

The D816V mutation changes the shape of the CD117 (CKIT) receptor and tells the mast cell to stay alive and encourage other mast cells to mature even when it shouldn’t.

Being CD117+ does not affect medication profile for mast cell disease at all. It just means it’s a mast cell. Some drugs are approved only for CKIT- patients (negative for D816V).

CD117/CKIT is a tyrosine kinase, which is a kind of protein. There are hundreds of known tyrosine kinases, CD117/CKIT is just one. Tyrosine kinase inhibitors can affect cells by blocking the signal to stay alive. Tyrosine kinases do not take up tyrosine from the environment, it has literally nothing to do with tyrosine metabolism at all.

If there any questions, ask in the comments.

8 Responses

  1. Rhonda Weiner April 25, 2016 / 11:27 am

    Hi Lisa,
    I have tested negative for the ckit mutation. I do have ism diagnosed by bone marrow biopsy, blood work and 24 hour urine. My baseline tryptase is 41, and my marrow showed a proliferation of mast cells as well as spindle shaped cells. My dr. (Cem Akin) said I probably am positive for the mutation–it just didn’t show up in the blood work. Can you clarify? Thank you.

    • Lisa Klimas April 25, 2016 / 2:26 pm

      Hi, Rhonda,

      Mast cells don’t live in the blood normally so there aren’t very many of them to find. If you have a room full of 1,000,000 balls and need to find the one green ball, it could take you forever, or you might not be able to find it. This is the same idea as what happens with this test. Because mast cells don’t live normally in the blood, you are looking for a mutation detected in very few cells in the blood, so it can be falsely negative. The test on the bone marrow is much more accurate.

  2. Madeline Ebels April 25, 2016 / 2:10 pm

    I have read in numerous studies in regards to various tumors, specifically GIST that CD117+ is an indication of treatment options and TKIs are recommended in this scenario. So I’m curious about why having CD117+ or as my results stated BRIGHT Positive this same thought process wouldn’t be considered. In BMB isn’t abnormal to find matured Mast Cells in general? I appreciate your time and thoroughly explained articles, the cardiology manifestations series has been extremely helpful to me!

    • Lisa Klimas April 25, 2016 / 2:23 pm

      Hi, Madeline,

      GIST tumors are not really related to mast cell disease, so we are comparing apples and oranges. GIST tumors are almost always CD117+ and may or may not be CKIT+ (for D816V or another mutation). GIST can be fatal without aggressive treatment (and often, with aggressive treatment). They are not mast cell tumors, but other type of cell that is expressing CD117. Because we know tyrosine kinase inhibitors can act at CD117/CKIT receptor, these medications are often used in GIST patients if the tumor cannot be resected.

      Having bright positive stain for mast cells in your bone marrow is normal. We expect there to be mast cells in the bone marrow. Brightness does not refer to how many cells there are, it refers to how strong a cell retained the stain. CD117 is also on mast cell progenitor cells normally, so a bright positive CD117 in bone marrow doesn’t mean anything unusual. Because it is a normal finding, it does not reflex to aggressive treatment.

  3. Deborah Ewing April 26, 2016 / 2:11 pm

    Lisa,
    Thank you so much for the CKIT information. I have theD816V mutation. My last BMB showed that 40% of my bone marrow is neoplastic
    Mast cells. I have gone through chemotherapy at the Huntsman Cancer Center and my tryptase level has gone down from 308 to 139.
    My question is this, I know mastinib has been proven to work in slowing down the CD117+ , I am wondering if any studies have successfully slowed down the D816V mutation?

  4. Sherry April 28, 2016 / 2:18 pm

    Do you have any information on CD25 expression on bone marrow?

    • Lisa Klimas April 29, 2016 / 11:10 am

      I do. Can you be more specific? CD25 is aberrant on mast cells but is normally found on other types of cells, like some T cells and B cells. On mast cells, it is a sign of systemic mastocytosis.

  5. Anna May 10, 2016 / 8:20 am

    Hi-
    This is the information from my BMB, can you explain what it means?

    Immunohistochemistry:
    Immunohistochemical stains (with adequate controls) on
    the core biopsy for
    CD34 and CD117 show no increase immature cells/blasts (<1%). Rare and
    scattered mast cells are positive for CD117 and Tryptase while negative
    for CD25
    CD25 and tryptase stained were preformed at Genpath.

    Thanks!

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