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Leukemia pathophysiology
Sometimes an immature blast cell have two gene mutations which prevent it from maturing into a specialized blood cell and cause it to multiply out of control. These immature blast cells crowd the bone marrow and impair the ability of the bones to make healthy blood cells. This leads to a decrease in platelets, red blood cells (RBCs) and white blood cells (WBCs). Created by Nauroz Syed.
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- At2:17, when the speaker says, "This a mature blood cell", wouldn't it be more accurate to say that "This is a mature white blood cell" or "This is a mature leukocyte", because she has previously instructed us that mature red blood cells do NOT have a nucleus like the mature blood cell depicted?(16 votes)
- No. Although mature erythrocytes (red blood cells) do not have nuclei, in the way she is explaining it, the cell has not completely differentiated at this point in hematopoiesis - i.e. it has not specialized into a leukocyte or erythrocyte or whatever it is told to be. However, the process of differentiation is not as black-and-white as presented.(17 votes)
- is acute myloid leukemia always fatal?(5 votes)
- There are treatments, so you can prevent death this way. Otherwise, "acute" means that it spreads quickly and ultimately, without prevention, it will cause death within just a few months.(3 votes)
- how does a blood cell mature(5 votes)
- Maturation in cells is equivalent to cell differentiation, when it becomes a cell with a specific function.(2 votes)
- Where does Leukemia get its name?(2 votes)
- leukos (greek) = white
haima (greek) = blood
Together, coined in German: Leukemia(5 votes)
- At9:33, what causes the mistake in cell division which leads to translocation of gene(3 votes)
- A mistake that is made during cell division where one part of the chromosome is shifted on to another chromosome.(1 vote)
- What are platelets?What are they made of? Why are they sometimes called dead cells?(1 vote)
- Platelets are like red cells in that they are little bags of enzymes waiting to be activated by the right triggers. Platelets are formed by large cells within the bone marrow called megakaryocytes. These cells have many nuclei, and grow in huge proportions to the rest of the developing blood cells. These cells then "die" and break off into little chunks, which we know to be platelets. Platelets have no nuclei, and do not reproduce outside of their primary production in the bone marrow.(4 votes)
- So what makes leukemia so deadly? I understand that it may take over one bone, but how does that cause such devastating effects in people?(2 votes)
- Leukemia is deadly because:
1.) Qualitatively defective WBC... which causes the patient to be suceptible to infection.
2.) It can cause Anemia
3.) It can cause Thrombocytopenia (low platelet count)(2 votes)
- does this happen to every body that has a sickness problem(1 vote)
- This video helped me learn more about Leukemia. Thank you so much!(2 votes)
- Leukemia is the most common cancer in children and teens but it's a very rare cancer overall(3 votes)
Video transcript
Voiceover: So, we talked a bit about the different types of cells
in the blood and how all of those cells are actually
made inside the bone marrow, so inside this cavity
in the center of bone. And, surprisingly, all of
these very very different cells actually come from, they
originate from, one cell, and that's this cell that
I'm drawing in over here, and as we talked about
before, this cell is called a hematopoietic stem cell, and this hematopoietic stem
cell is responsible for creating all of the
different cells in the blood, so instead of talking about it,
I'm just going to draw that. I'm going to draw this
hematopoietic stem cell creating a blood cell, and this could be any type of blood cell, but
we know that since the cell was just made, it was just
created, it's an immature cell. This is an immature blood cell, and we have a name for
immature blood cells. We call them blast cells. So, this is an immature blast cell, and these immature blast
cells are really big cells, and they have these really large nuclei. So, as you can see, the nucleus takes up pretty much the entire cell, and the DNA inside the nucleus is usually really loose and disorganized and kind
of all over the place, like I'm drawing it
over here, but the cell doesn't stay immature forever. Eventually, it moves along,
and it starts to mature, and as the cell matures, it gets smaller, so that's really
important, it gets smaller, and the nucleus inside the
cell also gets smaller, and you guys are probably
saying, well, obviously, as the cell gets smaller,
the nucleus inside it also has to get smaller,
but this is more than that. In this case, the nucleus
is actually taking up a smaller percentage of the cell. So, it's taking up less
room inside the cell, and even the DNA inside the
nucleus changes in appearance. It becomes a little bit more organized, a little bit more like
that, and then the cell continues to mature, and it passes through a couple more stages, until
it reaches its final stage, and when it reaches its final
stage, it's a lot smaller than when it started off, and the nucleus isn't nearly as large
as it was to begin with, and the DNA is really neatly packaged and compacted inside the cell's
nucleus, kind of like that. And so, this is a mature blood cell. This is a mature blood cell. And the process that I
just drew out over here is what normal blood cell
maturation looks like, and we throw that word around a lot. We talk about cell
maturation all the time. In fact, in this video,
I must have mentioned it like five or six times already,
but we rarely talk about why cells go through this
process of maturation. So, they go through this
process so that at the end, they can become specialized,
so they can become mature specialized cells,
and by specialized, I mean that the cell is able
to perform a specific task. So, for example, if we were looking at immature lymphoblasts over here, by the time they were finished
maturing into lymphocytes, they would be able to perform
certain immune functions. So, they'd be able to protect our body against invading organisms. So, that's the whole
purpose of cell maturation. So, this hematopoietic
stem cell continues to make more immature blood cells that then mature into these cells that
are able to do their job, and hematopoietic stem
cell does a really good job of doing that, so that we
end up with lots of new blood cells every single day,
but every once in a while, very rarely, actually, this
hematopoietic stem cell messes up, and it makes
an immature blast cell that's just weird, and it's not normal, and so that's the cell that
I'm drawing in over here, and this is the cell's
nucleus, and this is the DNA inside the nucleus, and
I know what I've drawn looks like a normal blast cell. In fact, it looks almost
identical to all the other immature blast cells that I've drawn, but it doesn't function
like a normal cell. Specifically, it doesn't
mature like a normal cell. So, it can't move on to the
next stage of development. It's almost as if there's
a stop sign over here, a stop sign, and so this
cell is stuck in the immature blast stage, right? And the reason why it's stuck,
is because there's a problem inside the cell, inside
the cell's nucleus, where one of these
genes or segments of DNA becomes mutated, and that gene is usually very important for
helping the cell mature, so that when the gene becomes mutated and it stops working
the way that it should, this cell then stops maturing
the way that it should. And that's the first thing
that happens in leukemia. This immature blast cell
loses the ability to mature, and if that was the
only thing that happened in leukemia, to be completely honest, it wouldn't be that big of a deal. So, if one cell can't
mature, it's really not the end of the world,
but then, unfortunately, this cell acquires another mutation, okay, and I'm putting that in a different color, and this time the mutation is in a gene that's really important for
controlling cell division, so that when that gene becomes mutated and it stops working
the way that it should, these cells lose control of
how many times they can divide, and that leads to a picture like this, where you end up with lots of these immature blast cells
accumulating and piling up, and as you can see, these
cells that are piling up have the same mutations as
that original weird blast cell, so they too are unable to mature, and they're dividing rapidly
and out of control, okay? So, when we talk about leukemia, this is the process that
we're talking about. We're talking about an
immature blast cell, right, our leukemic cell, that
first loses the ability to mature and then loses control over how many times it can
divide, and because of that, you end up with a situation
where you have lots and lots of these immature blast
cells and very few of these mature specialized cells, okay? And so, you guys might be saying, well, that's not a problem, the
hematopoietic stem cell can then just create some more
normal blast cells that'll mature and make up for
the shortage in our mature specialized cells, and
you'd be completely right. The hematopoietic stem
cells should be able to create more normal blast
cells, but it doesn't, and to explain why it
doesn't, we would have to take a look at bone marrow. So, imagine that we were
looking at bone marrow over here, and this was
a population or group of normal blood cells, and
then on this side we have our weird leukemic blast cells, okay, that we said aren't able to
mature, and we also said that they start dividing very rapidly, so that very quickly leads
to these leukemic cells taking over the bone marrow,
and that's a problem, because bone marrow is a contained cavity, so there's a very limited amount of space, nutrients, and growth
factors, and these cells inside the bone marrow
are constantly competing for these resources. So, as you can probably
imagine, if these leukemic cells are dividing really rapidly, they take up all of these resources for themselves, and they leave behind very little
for all the other cell types, and that's why the hematopoietic stem cell doesn't create more normal cells. It's because it doesn't have
the space, the nutrients, and the growth factors
to be able to do so. So, that's why when you have
a patient with leukemia, if you take a look
inside their bone marrow, you see that the bone marrow is almost overtaken by these leukemic blast cells, and you see a decrease in the number of all the other types of cells. So, you see a decrease in the
number of red blood cells, and you see a decrease in
the number of platelets, and decrease in the number
of white blood cells, and really this decrease in the number of all the other types
of cells is why leukemia is as devastating of a disease as it is. So, going back to our diagram over here, there's one big question,
one glaring question that I feel we haven't yet
addressed, and that is, number one, how does
a gene become mutated, and number two, how the
heck did this one cell end up with two gene mutations, okay? So, I want to talk about gene mutations and how you can get gene
mutations, off onto the side. And one of the causes of
gene mutation is something you may have heard of before, and that's exposure to
radiation, exposure to radiation, because we know radiation damages DNA. Another thing is exposure
to certain chemicals and toxins that also damage DNA, and those are called carcinogens. So, exposure to carcinogens
will also cause gene mutations, and both exposure to
radiation and carcinogens will usually cause an
isolated mutation in DNA. So, for example, if this
was a strand of DNA, and it was exposed to
radiation or carcinogens, you'd usually end up with
one gene being mutated, okay? A third thing that can
lead to gene mutation, that's really important
in the case of leukemia, is chromosome translocation, so, chromosome translocation,
and translocation is an error or mistake that's
made during cell division, where one part of a
chromosome becomes shifted or translocated onto another chromosome, so, something like that,
and because in this case we're messing around with
segments of chromosomes, you end up with multiple
genes being affected. So, instead of just one
gene, you can end up with mutations in two or more
genes, and lots of leukemias are associated with
chromosome translocation, and that's why this cell very easily ended up with two gene mutations. And that's how leukemia develops.