Published on August 16, 2021
Can One Mutated B Cell Lead to a CLL Diagnosis?
What happens when a single B cell mutates and becomes cancerous? In this segment, hosts Jeff Folloder and Michele Nadeem-Baker are joined by William Wierda, MD, PhD, and Nitin Jain, MD, from the MD Anderson Cancer Center as well as Farrukh Awan, MD, from the University of Texas Southwestern Medical Center to discuss how a singular cell mutation can eventually lead to a chronic lymphocytic leukemia (CLL) diagnosis.
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Transcript | The Biological Journey From One Mutated B Cell to a CLL Diagnosis
Jeff Folloder: I want to make sure that we touch a foundational element here, and that's by making sure we all understand exactly what CLL is. What we're going to do is imagine a time where our B cells were actually normal and healthy. This is a simple sketch of the start of a B cell. Dr. Jain, would you mind explaining what is going on here?
What Is a B Cell?
Dr. Jain: Sure, yeah. All of us have B cells. B cells are part of the normal immune system. And they help make antibodies, which help us fight infection, like bacterial infections and others. So, these B cells are actually made in the bone marrow that’s on the stem cell, and then they go some kind of a maturation process, then they leave the bone marrow, they go to the lymph node, and our lymph node like organs, like spleen and others, where they mature further, and then, they become what is called plasma cells and then make the antibodies. So that's like a normal B cell, that's what they do. That's the normal scenario, but in patients with CLL, at certain stage of the development of these cells, these cells become bad, get some more genetic abnormality, chromosome changes, and then they become like CLL cells.
What Happens When a Single B Cell is Mutated?
Dr. Wierda: So something becomes disrupted in one individual cell, one individual B cell, and it causes that B cell to grow, not under the regular control mechanisms that the immune system in the body uses, but independent of those. And in doing that, the cells grow, and divide, and multiply. And that one cell becomes many, many, many, many, many cells that collect in the blood, and the bone marrow, and the lymph nodes. They do die, but they have a prolonged lifespan. They don't do the normal things that B cells should do, like get activated by invading organisms and make antibodies. They can be activated, but activated cells in this sense are not a good thing because it indicates that they may be dividing more rapidly and growing more rapidly and not dying. Basically they're one single cell that has gone awry, that doesn't behave like it's supposed to in the body, and grows, and collects in various organs.
Michele Nadeem-Baker: A question that we have is, are there two different places a cell can become cancerous, can be corrupt?
Dr. Awan: Yes. They can be corrupted in the bone marrow, they can be corrupted in the spleen, they can be corrupted in the lymph nodes. And they take the highway, the freeway from one point to another, which is your blood. And you can test any of those areas. You can actually put a needle in the police station and get a sample from the lymph node. You can put a needle in the blood which is the easiest, or you can go straight from the factory and put a needle in the bone marrow.
Jeff Folloder: No, thank you. No, thank you. We don't like those bone marrow biopsies.
Michele Nadeem-Baker: Oh my gosh.
Dr. Jain: It is not painful, it's uncomfortable.
Michele Nadeem-Baker: Oh, it is. Have you had one, doctor?
Dr. Jain: Everybody asked me that. No, I have not. I have had multiple patients that say that it's not painful, it's uncomfortable, yeah.
Michele Nadeem-Baker: Dr. Jain, how about explaining to our audience, what happens then? What happens when all this is happening in our body, right? And we have things our B cells are becoming cancerous. So then, what does that do to us?
Dr. Jain: Yeah. Obviously, it takes a while, right? You have one cell which becomes abnormal. Cancer cell beats CLL cell. And then one cell leads to two cells, two cells lead to four cells, they kind of multiply for years, and months and months. And you know, likely several years before they are a sufficient number, because as they start growing, they start growing in the lymph nodes, they start growing in the bone marrow, they start growing in the liver and spleen. And as Dr. Awan was saying, because everything is connected by blood, right? So these are not totally separate isolated areas. So you're going to have patients with mostly in the lymph nodes and sometimes we call them SLL. And that may be a certain discussion point we can discuss later as well. Many patients have in the blood and the bone marrow, and that's really when we use it on CLL, which is a more common term to use.
What Are the Early Symptoms of Chronic Lymphocytic Leukemia (CLL)?
Early on patients may not feel anything. And actually, I think the most common reason I see in the practice is patients go to the local doctor, primary care doctor. They have a routine blood test, and their white blood cell count is 15,000 and doctors said, "Oh, you know, let's just check it again in two months, three months." "Oh, it's 17,000. Okay. Let's send you to hematologist." You have CLL. But they have no symptoms whatsoever. And it was really just a routine blood count which was done. And that's how many times it comes into the picture. So early-stage patients have no symptoms, but as the disease starts growing, build up more in the lymph nodes, build up more in the bone marrow, you may start feeling it in the lymph nodes, which they can feel in the neck, in the armpits, groin area.
And then as the bone marrow gets involved more and more, bone marrow has a lot of reserve. So you can have quite a bit of disease in the bone marrow without affecting your normal blood counts. Because our bone marrow has a lot of reserve to make blood and platelets, but really when it becomes quite involved, then we start having low blood counts, and the white blood cell count rises, but the platelets and the hemoglobin starts dropping. And that's where kind of more symptoms from the disease starts coming along. Things, we call it B symptoms, night sweats, weight loss, low-grade fevers, just not feeling well. And then you're going to have symptoms from low hemoglobin as well; like shortness of breath, you cannot go up a flight of stairs, just feeling tired and fatigue. It takes a while from a single cell which become abnormal to the actual diagnosis of CLL. And then from the diagnosis of CLL, it's another journey some years before you need treatment for your CLL, when you start manifesting all the symptoms from the accumulation of these cells.